Name: 10534-59-5|Tetrabutylammonium acetate|98% (contains 10-15%AcOH)
Brand: Ambeed
SKU: A162456
Price: 5.0 USD
Availability: InStock
Rating: 99 (25 reviews)

1
[ 4455-09-8 ]
[ 10534-59-5 ]
[ 103-45-7 ]

Reference： [1]Journal of the American Chemical Society,1971,vol. 93,p. 4735 - 4749

2
[ 592-76-7 ]
[ 10534-59-5 ]
[ 7182-86-7 ]
[ 5401-62-7 ]
[ 5837-71-8 ]
[ 5433-23-8 ]

Reference： [1]Journal of Organic Chemistry USSR (English Translation),1984,vol. 20,p. 205 - 213
Zhurnal Organicheskoi Khimii,1984,vol. 20,p. 233 - 242

3
[ 10534-59-5 ]
5-butyl-2,2-dimethyl-1,4-dioxaspiro<2.2>pentane [ No CAS ]
[ 113403-72-8 ]

Yield	Reaction Conditions	Operation in experiment
93%	With acetic acid In tetrahydrofuran at 0℃; for 0.25h;

Reference： [1]Crandall, Jack K.; Batal, David J.; Sebesta, David P.; Lin, Feng [Journal of Organic Chemistry, 1991, vol. 56, # 3, p. 1153 - 1166]

4
[ 10534-59-5 ]
[ 99-73-0 ]
[ 7500-37-0 ]

Reference： [1]Tetrahedron,1994,vol. 50,p. 10539 - 10548

5
[ 10534-59-5 ]
(phenoxymethyl)diazirine [ No CAS ]
[ 154197-56-5 ]

Yield	Reaction Conditions	Operation in experiment
42%	With air In N,N-dimethyl-formamide at 21℃; for 0.166667h;

Reference： [1]Moss, Robert A.; Xue, Song; Liu, Weiguo; Krogh-Jespersen, Karsten [Journal of the American Chemical Society, 1996, vol. 118, # 50, p. 12588 - 12597]

6
[ 10534-59-5 ]
[ 467242-36-0 ]
[ 467242-34-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With lithium chloride In dimethyl sulfoxide at 60℃;

Reference： [1]Thominiaux, Cyrille; Chiaroni, Angèle; Desmaële, Didier [Tetrahedron Letters, 2002, vol. 43, # 22, p. 4107 - 4110]

7
[ 10534-59-5 ]
[ 701261-73-6 ]
[ 522602-70-6 ]

Yield	Reaction Conditions	Operation in experiment
78%	In toluene at 40 - 50℃; for 2h;

Reference： [1]Hanessian, Stephen; Tremblay, Martin; Petersen, Jens F. W. [Journal of the American Chemical Society, 2004, vol. 126, # 19, p. 6064 - 6071] Hanessian, Stephen; Tremblay, Martin [Organic Letters, 2004, vol. 6, # 25, p. 4683 - 4686]

8
[ 75-09-2 ]
[ 10534-59-5 ]
[ 628-51-3 ]

Reference： [1]Tetrahedron Asymmetry,2006,vol. 17,p. 1561 - 1567

9
[ 912478-19-4 ]
[ 10534-59-5 ]
[ 912478-21-8 ]

Yield	Reaction Conditions	Operation in experiment
64%	Stage #1: phenyl 2,3-O-(2',3'-dimethoxy-2',3'-dimethylbutane)-1-thio-β-L-fucopyranoside With trifluoromethanesulfonic acid anhydride In pyridine; dichloromethane at -40℃; for 0.5h; Stage #2: tetrabutylammonium acetate In toluene for 24h; sonication;

Reference： [1]Rabuka, David; Hubbard, Sarah C.; Laughlin, Scott T.; Argade, Sulabha P.; Bertozzi, Carolyn R. [Journal of the American Chemical Society, 2006, vol. 128, # 37, p. 12078 - 12079]

10
C₃₀H₄₄O₁₀Si [ No CAS ]
[ 10534-59-5 ]
[ 917113-32-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: C₃₀H₄₄O₁₀Si With titanium(IV) isopropylate In dichloromethane at 20℃; for 0.5h; Stage #2: tetrabutylammonium acetate In dichloromethane at 20℃; for 10h; Further stages.;

Reference： [1]Lei, Xiaoguang; Porco Jr., John A. [Journal of the American Chemical Society, 2006, vol. 128, # 46, p. 14790 - 14791]

11
[ 10534-59-5 ]
[ 244023-84-5 ]
1-acetoxy-4-hydroxy-3-phenylbutan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With acetic acid In tetrahydrofuran at 0 - 20℃;

Reference： [1]Howell, Amy R.; Ndakala, Albert J. [Organic Letters, 1999, vol. 1, # 6, p. 825 - 827]

12
[ 10534-59-5 ]
[ 165727-45-7 ]
[ 180713-67-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	In acetonitrile; for 18h;Heating / reflux;	Example 1 (2S, 3S)-1-Acetoxy-3-(t-butoxycarbonylamino)-2-hydroxy-4-phenylbutane A mixture composed of 2.0 mmol (0.599 g) of <strong>[165727-45-7](2S, 3S)-3-(t-butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane</strong>, 2.4 mmol (0.724 g) of tetrabutylammonium acetate and 10 ml of acetonitrile was stirred under reflux for 18hours.. Thereafter, the solvent was distilled off under reduced pressure, 20 ml of water and 20 ml of ethyl acetate were added, and the organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude product.. This was dissolved in 10 ml of methanol with heating and the solution was cooled and allowed to stand.. The resulting crystalline precipitate was collected by filtration, whereupon 0.449 g (70%) of the title compound was obtained. 1H-NMR (400 MHz, CDCl3) delta 1. 37 (s, 9H), 2.11 (s, 3H), 2.84-2.97 (m, 2H), 3.36 (br, 1H), 3.88-3.91 (m, 2H), 4.12 (dd, 1H, J=11.7 Hz, 3.2 Hz), 4.59-4.76 (m, 1H), 7.20-7.32 (m, 5H). 13C-NMR (100 MHz, CDCl3) delta 20.92, 28.23, 36.01, 54.24 66.24, 71.87, 80.01, 126.63, 128.57, 129.39, 137.42, 156.11, 171.34.
	In methanol; water; ethyl acetate; acetonitrile;	Example 1 (2S,3S)-1-Acetoxy-3-(t-butoxycarbonylamino)-2-hydroxy-4-phenylbutane A mixture composed of 2.0 mmol (0.599 g) of (2S,3S)-3-(t-butoxycarbonylamino)-1-chloro-2-hydroxy-4-phenylbutane, 2.4 mmol (0.724 g) of tetrabutylammonium acetate and 10 ml of acetonitrile was stirred under reflux for 18 hours. Thereafter, the solvent was distilled off under reduced pressure, 20 ml of water and 20 ml of ethyl acetate were added, and the organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude product. This was dissolved in 10 ml of methanol with heating and the solution was cooled and allowed to stand. The resulting crystalline precipitate was collected by filtration, whereupon 0.449 g (70%) of the title compound was obtained. 1H-NMR (400 MHz, CDCl3) delta 1.37 (s, 9H), 2.11 (s, 3H), 2.84-2.97 (m, 2H), 3.36 (br, 1H), 3.88-3.91 (m, 2H), 4.12 (dd, 1H, J=11.7 Hz, 3.2 Hz), 4.59-4.76 (m, 1H), 7.20-7.32 (m, 5H). 13C-NMR (100 MHz, CDCl3) delta 20.92, 28.23, 36.01, 54.24, 66.24, 71.87, 80.01, 126.63, 128.57, 129.39, 137.42, 156.11, 171.34.

Reference： [1]Patent: US6348615,2002,B2 .Location in patent: Page column 5
[2]Patent: US6278002,2001,B1

13
[ 10534-59-5 ]
(1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester [ No CAS ]
[ 180713-67-1 ]

Yield	Reaction Conditions	Operation in experiment
64%	With acetic acid In acetonitrile for 18h; Heating / reflux;	2 Example 2; (2S, 3S) -1-Acetoxy-3-(t-butoxycarbonylamino) -2-hydroxy-4-phenylbutane Example 2 (2S, 3S) -1-Acetoxy-3-(t-butoxycarbonylamino) -2-hydroxy-4-phenylbutane A mixture composed of 2.0 nmmol (0.524 g) of (2S, 3S)-3-(t-butoxycarbonylamino)-4-phenylbutane-1,2-epoxide, 2.4 mmol (0.724 g) of tetrabutylammonium acetate, 4.0 mmol (0.24 g) of acetic acid and 10 ml of acetonitrile was stirred under reflux for 18 hours.. Thereafter, the solvent was distilled off under reduced pressure, 20 ml of water and 20 ml of ethyl acetate were added, and the organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude product.. Purification by silica gel column chromatography gave 0.415 g (64%) of the title compound.
0.415 g (64%)	With acetic acid In water; ethyl acetate; acetonitrile	2 (2S,3S)-1-Acetoxy-3-(t-butoxycarbonylamino)-2-hydroxy-4-phenylbutane Example 2 (2S,3S)-1-Acetoxy-3-(t-butoxycarbonylamino)-2-hydroxy-4-phenylbutane A mixture composed of 2.0 mmol (0.524 g) of (2S,3S)-3-(t-butoxycarbonylamino)-4-phenylbutane-1,2-epoxide, 2.4 mmol (0.724 g) of tetrabutylammonium acetate, 4.0 mmol (0.24 g) of acetic acid and 10 ml of acetonitrile was stirred under reflux for 18 hours. Thereafter, the solvent was distilled off under reduced pressure, 20 ml of water and 20 ml of ethyl acetate were added, and the organic layer was separated, dried over sodium sulfate, filtered and concentrated under reduced pressure to give a crude product. Purification by silica gel column chromatography gave 0.415 g (64%) of the title compound.

Reference： [1]Current Patent Assignee: KANEKA CORPORATION - US6348615, 2002, B2 Location in patent: Page column 5-6
[2]Current Patent Assignee: KANEKA CORPORATION - US6278002, 2001, B1

14
(+)-7-bromo-dimethoxy-CBD [ No CAS ]
[ 10534-59-5 ]
(+)-7-acetoxy-dimethoxy-CBD [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	In acetone for 2h; Heating / reflux;	11 (8a) (570 mg, 1.35 mmol) was dissolved in acetone (15moi, stored on 4A° molecular sieves) and tetrabutylammonium acetate ((NBU) 4NH4OAC) (450mg, 1.49 mmol). The mixture was stirred, refluxed and monitored by TLC (20% ETHER/P. E. ). After 2 hours there was no more starting material. The acetone was removed under reduced pressure, and the residue was diluted with water (20 ml) and extracted with ether. The combine organic extracts were washed with aqueous sodium bicarbonate and brine, dried on MGS04 and filtered. Removal of the solvents under reduced pressure afforded 520 mg of an oily residue (96% yield). (9a): 1H-NMR & 6.320 (2H, s, Ar), 5. 581 (1H, s, olefin), 4.492-4. 386 (4H, m, CHAOAC + olefin), 4.040-3. 986 (1H, m, benzyl), 3.715 (6H, s, OCH3), 2.853- 2.801 (1H, m), 2.195-2. 071 (2H, m), 2.060 (3H, s, OAc), 1.823-1. 695 (2H, m), 1.605 (5H, br s), 1.323 (4H, br s), 0.921-0. 875 (3H, t, J=6.7 Hz, terminal CH3). IR : 2900,1720, 1580,1440, 1110 CM-1. [a] D: +135. 2° (c 15. 95 mg/ml, CHCl3)

Reference： [1]Current Patent Assignee: ARIEL (unclear) - WO2005/23741, 2005, A2 Location in patent: Page/Page column 24-25

15
[ 866088-07-5 ]
[ 10534-59-5 ]
[ 866088-08-6 ]

Yield	Reaction Conditions	Operation in experiment
95%	In 1-methyl-pyrrolidin-2-one at 100℃; for 24h;	3 To a 3-litre three necked round bottomed flask flushed with dry nitrogen the O- benzyl-chlorolactol methyl acetal (30g) was charged into dry N-methyl pyrollidinone (756mis). Anhydrous tetrabutylammonium acetate (102.57g) was also charged to the solution. The reaction mixture was then heated at 100°C for 24 hours. The reaction mixture was sampled at routine intervals and directly analysed by tlc and gc/ms. The black solution was then diluted with water (150mis) and extracted with ethyl acetate (3 x 1500mis). The combined upper organic layer was then washed with water (3 x 1500mls). The aqueous portion showed no product content at this point. The layers were then separated, dried, (Na2SO4) and the solvent removed in vacuo to yield a black flowing oil (31g, 95%) containing a mixture of anomers.'H nmr CDCI31. 4-1.8 (m 4H), 2.0- 2.1 (duplicate s, 3H), 3.4 & 3.5 (s 3H), 3.8 (m 1H), 4.0 (m 1H), 4.1 (m 2H), 4.5 (m, 2H), 4.7-4. 9 (m 1H), 7.2-7. 3 (m, 5H) ; 13C nmr CDCI3 20.8 ; 30-35; 55&56; 57&64; 66&68; 69&72; 70&71; 98&99; 127-128 & 138; 170.5 ; m/z 293,262, 221,203, 156,91 and 43.

Reference： [1]Current Patent Assignee: REDX PHARMA PLC - WO2005/92867, 2005, A2 Location in patent: Page/Page column 7

16
chloride (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester [ No CAS ]
[ 10534-59-5 ]
[ 124655-09-0 ]
[ 154026-95-6 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one;	(a) (4R-cis)-6-[(Acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester STR32 Solid tetra-n-butylammonium acetate prepared in step (e)(i) of Example 1 above (106.2 g, 0.352 mole) was added in one portion to a mechanically stirred solution of the chloride (4R-cis)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester prepared in step (d) of Example 1 above (32.7 g, 0.117 mole) in HPLC grade 1-methyl-2-pyrrolidinone (471 ml) under argon. The resulting solution was stirred at 85 C. (internal temperature). After 30 to 60 minutes the reaction mixture became homogeneous and brown in color. The progress of the reaction was followed by TLC and GC analysis. (TLC: Rf =0.54 for the title compound; Rf =0.63 for the chloride starting material (silica gel, Ethyl acetate:Hexane, 1:1, visualization by Ce(SO4)2 spray).) After 9 hours the reaction was completed. The reaction mixture was cooled to room temperature and poured into water (4 L) and extracted with heptane (31L). The organic layers were combined and washed with water (1L), brine, dried over MgSO4, filtered and concentrated under reduced pressure to furnish 31.5 grams of a brown solid. It was dissolved in heptane (500 ml) and treated with neutral NORIT (40 grams). The heterogeneous solution was boiled on a water bath for a few minutes and filtered hot through a celite bed on a Buchner funnel. The residue was washed with hot heptane (3250 ml). The filtrates were combined and concentrated on a rotary evaporator under reduced pressure to afford the title compound as a light yellow solid (31.1 grams). This solid was dissolved in hot heptane (60 ml) and allowed to cool slowly to room temperature.

Reference： [1]Patent: US5278313,1994,A

17
[ 10534-59-5 ]
[ 74866-37-8 ]
2-phenyl-3-phenylsulphonyl-1,2-propanediol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With tert.-butylhydroperoxide; sodium hydrogen sulfate; sodium chloride In acetone	62 EXAMPLE 62 (according to process K) EXAMPLE 62 (according to process K) 2-Phenyl-1-phenylsulphonyl-2-propene (5.16 g, 0.02 mole) is dissolved in acetone (40 cc). Tetrabutylammonium acetate (1.3 g, 0.005 mole) and 70% strength tert-butyl hydroperoxide (4.4 cc, 0.03 mole) are added and the mixture is stirred at ambient temperature for 15 h. Ether (80 cc) is added, the mixture is cooled to 0° C. and a 10% strength NaHSO3 solution (10 cc) is added in one lot. After 1 h stirring, the two phases are separated, the aqueous phase is saturated with NaCl (4 g) and is reextracted with ether (2*25 cc) and the combined organic phases are washed with brine (50 cc) and dried over MgSO4. The crystallized crude (5.5 g) is recrystallized from acetone to give white crystals of 2-phenyl-3-phenylsulphonyl-1,2-propanediol (3.6 g, 61%). Mp=137° C.

Reference： [1]Current Patent Assignee: BAYER AG; SOLVAY - US5100460, 1992, A

18
[ 69861-71-8 ]
[ 10534-59-5 ]
Pd⁽¹⁺⁾*CH₃CO₂^(1-)*P(C₆H₄CH₃)3=(CH₃CO₂)Pd(P(C₆H₄CH₃)3) [ No CAS ]

Reference： [1]Journal of Organometallic Chemistry,1999,vol. 576,p. 23 - 41

19
[ 616-42-2 ]
[ 10534-59-5 ]
tetrabutylammonium methylsulfite [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	at 20℃; for 91h;	5 Example 5 Tetrabutylammonium Methylsulfite A mixture of 1.84 g (6.1 mmol) of tetrabutylammonium acetate and 0.672 g (6.1 mmol) of dimethyl sulfite is stirred at room temperature for 91 hours under an inert-gas atmosphere (nitrogen) in a sealed reaction vessel. The end of the reaction is determined by NMR measurement. The product is pumped off over the course of 2 hours in vacuo at 13.3 Pa and room temperature, giving 1.98 g of liquid tetrabutylammonium methylsulfite. The yield is virtually quantitative. The product is investigated by means of NMR spectroscopy. 1H NMR (reference: TMS; solvent: CD3CN), ppm: 0.95 t (4CH3); 1.34 t, q (4CH2); 1.60 m (4CH2); 3.10 m (4CH2); 3.15 s (CH3O); 3JH,H=7.4 Hz.

Reference： [1]Current Patent Assignee: MERCK KGAA - US2008/227987, 2008, A1 Location in patent: Page/Page column 8

20
[ 616-42-2 ]
[ 10534-59-5 ]
[ 919788-71-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	at 20℃; for 116h;	6 Example 6 Tetrabutylammonium Ethylsulfite A mixture of 3.69 g (12.2 mmol) of tetrabutylammonium acetate and 0.672 g (12.2 mmol) of dimethyl sulfite is stirred at room temperature for 116 hours under an inert-gas atmosphere (nitrogen) in a sealed reaction vessel. The end of the reaction is determined by NMR measurement. The product is pumped off over the course of 3 hours in vacuo at 13.3 Pa and room temperature, giving 4.19 g of liquid tetrabutylammonium ethylsulfite. The yield is virtually quantitative. The product is investigated by means of NMR spectroscopy. 1H NMR (reference: TMS; solvent: CD3CN), ppm: 0.90 t (4CH3); 1.06 t (CH3); 1.33 t,q (4CH2); 1.60 m (4CH2); 3.13 m (4CH2); 3.52 q (CH2O); 3JH,H=7.4 Hz.

Reference： [1]Current Patent Assignee: MERCK KGAA - US2008/227987, 2008, A1 Location in patent: Page/Page column 8

21
[ 1032314-91-2 ]
[ 10534-59-5 ]
[ 1032314-93-4 ]

Yield	Reaction Conditions	Operation in experiment
48%	With cobalt acetylacetonate In benzene at 90℃; for 24h;

Reference： [1]Shenvi, Ryan A.; Guerrero, Carlos A.; Shi, Jun; Li, Chuang-Chuang; Baran, Phil S. [Journal of the American Chemical Society, 2008, vol. 130, # 23, p. 7241 - 7243]

22
para-methoxyphenyl {3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-2)]-3,6-di-benzyl-α-D-mannopyranosyl-(1-3)}-4,6-O-benzylidene-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[2,3,4-tri-O-benzyl-α-L-fucopyranosyl-(1-6)]-3-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]
[ 10534-59-5 ]
para-methoxyphenyl {3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-2)]-3,6-di-O-benzyl-α-D-mannopyranosyl-(1-3)}-4,6-O-benzylidene-2-O-acetyl-O-D-mannopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[2,3,4-tri-O-benzyl-α-L-fucopyranosyl-(1-6)]-3-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: para-methoxyphenyl {3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-2)]-3,6-di-benzyl-α-D-mannopyranosyl-(1-3)}-4,6-O-benzylidene-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-[2,3,4-tri-O-benzyl-α-L-fucopyranosyl-(1-6)]-3-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0 - 20℃; for 6.5h; Stage #2: tetrabutylammonium acetate In toluene for 20h; Sonographic reaction;	39 para-Methoxyphenyl {3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1→4)-[3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1→2)]-3,6-di-O-benzyl-α-D-mannopyranosyl-(1→3)}-4,6-O-benzylidene-2-O-acetyl-O-D-mannopyranosyl-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1→4)-[2,3,4-tri-O-benzyl-α-L-fucopyranosyl-(1→6)]-3-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside Pyridine (1.05 g) was added to compound 38 (0.75 g) in dichloromethane (15 mL) under argon. The mixture was stirred and cooled to 0° C. and triflic anhydride (1.12 g) added dropwise. After 30 minutes the mixture was warmed to room temperature and stirred for 6 hours. Dichloromethane was added and the mixture washed with saturated sodium hydrogen carbonate and dried (MgSO4). Tetrabutylammonium acetate (1.12 g) and dry toluene (20 mL) were added and the reaction vessel placed in a sonic bath for 20 hours after which the mixture was chromatographed [SiO2, ethyl acetate:petrol (50:50) to (60:40)] to give compound 39 (0.573 g).

Reference： [1]Current Patent Assignee: GLYCOFORM LIMITED - US2009/176970, 2009, A1 Location in patent: Page/Page column 10

23
para-methoxyphenyl 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl-(1-3)-4,6-O-benzylidene-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]
[ 10534-59-5 ]
para-methoxyphenyl 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl-(1-3)-4,6-O-benzylidene-2-O-acetyl-β-D-mannopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: para-methoxyphenyl 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl-(1-3)-4,6-O-benzylidene-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0 - 20℃; for 2h; Stage #2: tetrabutylammonium acetate In toluene for 16h; Sonographic reaction;	72 para-Methoxyphenyl 2-O-acetyl-3,4,6-tri-O-benzyl-α-D-mannopyranosyl-(1→3)-4,6-O-benzylidene-2-O-acetyl-β-D-mannopyranosyl-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl-(1-4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside Compound 71 (4.4 g) and anhydrous pyridine (6.3 mL) were dissolved in dichloromethane (50 mL). The mixture was cooled to 0° C. and triflic anhydride (5.6 mL) was added. The mixture was allowed to warm to room temperature over 2 hours and dichloromethane and saturated sodium hydrogen carbonate were added. The organic phase was separated, dried (MgSO4) and evaporated under reduced pressure. Toluene (100 mL) and tetra-butylammonium acetate (5.1 g) were added and the reaction vessel placed in a sonic bath for 16 hours. The mixture was evaporated under reduced pressure and chromatographed [SiO2, ethyl acetate:petrol (50:50)] to give compound 72 (3.0 g).

Reference： [1]Current Patent Assignee: GLYCOFORM LIMITED - US2009/176970, 2009, A1 Location in patent: Page/Page column 22-23

24
[ 2052-49-5 ]
[ 64-19-7 ]
[ 10534-59-5 ]

Yield	Reaction Conditions	Operation in experiment
81%	In methanol at 20℃;
	In methanol
	In methanol	General procedure: Tetrabutylammonium salts of anions were prepared by the addition of 1 equivof Bu4NOH to 1 equiv of a carboxylic acid or amino acid dissolved in the MeOH.After evaporating the MeOH in vacuo, the salts were dried under high vacuumover P2O5.

	In ethanol for 1h;	Ethanol 7.1 g and acetic acid 1.12 g (18.6 mmol, 1.2 eq)Were mixed to prepare an acetic acid solution. The above-mentioned TBAOH mixed solution was placed in an ice bath,An acetic acid solution was added dropwise thereto over 5 minutes,And the mixture was stirred for 1 hour. after that,Using a rotary evaporator,Ethanol and acetic acid were removed. thus,Tetrabutylammonium acetate (TBAA) was obtained. Incidentally,At this point, since tetrabutylammonium acetate and potassium acetate are mixed, 11.6 g of dimethylsulfoxide is further added,The precipitated potassium acetate was removed by suction filtration. further,Using a vacuum pump,Remaining ethanol and water were also removed. From the above,To obtain a mixed solution of tetrabutylammonium acetate and dimethylsulfoxide (3.1-TBAA solution).
	In water
	In methanol	4.3. Titration Experiments General procedure: Tetrabutylammonium (TBA) salts of examinate anions were prepared before every titrationexperiments, namely commercially available carboxylic acid (from Sigma Aldrich or TCI Europe) wasdissolved in 0.5 mL of dry methanol and one equivalent of TBAOH (solution in methanol, c = 1.21 M)was added. Prior to the experiment, the salts were pre-dried overnight under high vacuum at 60 °C.To obtain the appropriate water concentration distilled water was added to the commercially availableDMSO-d6 or acetone-d6 of 99.9% isotopic purity. All titration experiments was performed on Bruker(400 MHz) at 298K.

Reference： [1]Nagae, Haruki; Aoki, Ryota; Akutagawa, Shin-Nosuke; Kleemann, Julian; Tagawa, Risa; Schindler, Tobias; Choi, Gyeongshin; Spaniol, Thomas P.; Tsurugi, Hayato; Okuda, Jun; Mashima, Kazushi [Angewandte Chemie - International Edition, 2018, vol. 57, # 9, p. 2492 - 2496][Angew. Chem., 2018, vol. 130, # 9, p. 2518 - 2522,5]
[2]Denmark, Scott E.; Burk, Matthew T.; Hoover, Andrew J. [Journal of the American Chemical Society, 2010, vol. 132, p. 1232 - 1233]
[3]Hamankiewicz, Paulina; Granda, Jarosław M.; Jurczak, Janusz [Tetrahedron Letters, 2013, vol. 54, # 41, p. 5608 - 5611]
[4]Current Patent Assignee: FUTAMURA CHEMICAL CO., LTD. - JP2016/44149, 2016, A Location in patent: Paragraph 0069
[5]Hooe, Shelby L.; Rheingold, Arnold L.; MacHan, Charles W. [Journal of the American Chemical Society, 2018, vol. 140, # 9, p. 3232 - 3241]
[6]Tyszka-Gumkowska, Agata; Pikus, Grzegorz; Jurczak, Janusz [Molecules, 2019, vol. 24, # 14]

25
([2.2]paracyclophan-4-yl)(4'-methoxyphenyl)iodonium hexafluorophosphate [ No CAS ]
[ 10534-59-5 ]
[ 696-62-8 ]
[ 1200-06-2 ]
[ 24261-99-2 ]
[ 5628-13-7 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 4079 - 4083

26
(thiene-2-yl)(4'-methoxyphenyl)iodonium trifluoracetate [ No CAS ]
[ 10534-59-5 ]
[ 3437-95-4 ]
[ 696-62-8 ]
[ 1200-06-2 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 4079 - 4083

27
(7-methoxy[2.2]paracyclophan-4-yl)(4'-methoxyphenyl)iodonium hexafluorophosphate [ No CAS ]
[ 10534-59-5 ]
[ 696-62-8 ]
[ 1200-06-2 ]
[ 1235887-94-1 ]

Reference： [1]Angewandte Chemie - International Edition,2010,vol. 49,p. 4079 - 4083

28
[ 10534-59-5 ]
[ 100-52-7 ]
[ 3480-87-3 ]

Reference： [1]Journal of Organic Chemistry,2010,vol. 75,p. 5351 - 5354

29
[ 60511-85-5 ]
[ 10534-59-5 ]
C₂H₃O₂^(1-)*C₁₆H₃₆N⁽¹⁺⁾*C₁₈H₁₂N₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2010,vol. 8,p. 4811 - 4814

30
[ 10534-59-5 ]
[ 154026-94-5 ]
[ 154026-95-6 ]

Yield	Reaction Conditions	Operation in experiment
99.1%	at 115℃; for 7h;	Example 8 - Preparation of tert-butyl 2-[(4R,6S)-2,2-dimethyl-6-[(rnethyl- carbonyloxy)methyl]-1 ,3-dioxan-4-yl]acetate from tetra-n-butyl ammonium acetateIn a 100ml_ round vessel was added crude tert-butyl 2-[(4R,6S)-6-(chloromethyl)- 2,2-dimethyl-1 ,3-dioxan-4-yl]acetate (5.0g) and tetra-n-butyl ammonium acetate (4.3g). The mixture was heated to 115C and became liquid at ~50C. The mixture was heated for 7 hours.Heptane (15mL) was added to the reaction and the mixture stirred for 5 minutes at 70C before decanting the heptane phase. The mixture was further extracted with heptane (2 x 10ml_) at 70C. The combined heptane extracts were washed with water (10mL) and then filtered through a bed of celite filter aid. The heptane filtrate was partially evaporated then cooled to -10C. The pale yellow crystals were filtered and dried, yield = 1.1g with a purity of 99.1 % by HPLC.
7.2 g	In 1-methyl-pyrrolidin-2-one; at 25 - 95℃; for 24h;	To a solution of ieri-butyl 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-l,3-dioxan-4- yl)acetate (10 g) in NMP (300 mL) was added tetra butyl ammonium acetate (30 g) at 25C. Resulting reaction mixture was heated to 95C and stirred for 24 h. After cooling to room temperature, water (450 mL) was added and then extracted with n-heptane (3 X 150 mL). To the combined organic layer was added activated charcoal (1 g) and stirred for 5 h, filtered the activated charcoal and filtrate was concentrated to obtained crude product, which was further recrystallized from n-heptane to obtain off white solid material (7.2g, 99.2% GC purity and 99.5% de). Gas Chromatographic system: Instrument : Gas Chromatograph equipped with FID detector. Column : DB-5, length: 30 mtr. , Dia.: 0.53mm, 5.0muiotaeta Capillary Column. Detector : Flame Ionization Detector. Carrier gas : Nitrogen. Gas Chromatograph parameters: Carrier gas pressure : 8.0 psi. Detector Temperature : 280C Injector Temperature : 280C Injection volume Split ratio Retention time: Approximate retention time for compound [XI] is about 12.0 min

Reference： [1]Patent: WO2012/17242,2012,A1 .Location in patent: Page/Page column 20
[2]Patent: WO2014/203045,2014,A1 .Location in patent: Page/Page column 43; 44

31
[ 1380664-98-1 ]
[ 10534-59-5 ]
[ 1380665-17-7 ]

Yield	Reaction Conditions	Operation in experiment
100%	In dimethyl sulfoxide at 80℃; for 72h;	38 Intermediate 38; Carbamic acid, N-[7-[(acetyloxy)methyl]-2-[[[(4-fluoro-3- methylphenyl)methyl] amino] carbonyl] -6, 7, 8,9-tetrahydro-3-hydroxy-4-oxo-7, 10- ethanopyrimido[l,2-a]azepin-10(4H)-yl]-, phenylmethyl ester. A solution of carbamic acid, [2-[[[(4-fluoro-3-methylphenyl)methyl]amino]carbonyl]-6,7,8,9- tetrahydro-3-hydroxy-7-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-4-oxo-7,10- ethanopyrimido[l,2-a]azepin-10(4H)-yl]-, phenylmethyl ester, Intermediate 37, (6.24 g, 8.85 mmol, 1 equiv) and tetrabutylammonium acetate (21.4 g, 70.8 mmol, 8 equiv) in DMSO (89 mL) was heated to 80 °C (oil bath) for 3 d. Upon completion, the reaction was added to 1 N HC1 and extract with EtOAc (x 2). The combined EtOAc layers were washed with brine, dried ( a2S04), and concentrated in vacuo to give the title compound as a brown solid (5.82 g, -100%). XH NMR (400 MHz, CDC13) δ ppm 12.01 (1 H, br. s.), 7.60 (1 H, br. s.), 7.31 - 7.42 (5 H, m), 7.01 (3 H, br. s.), 4.93 (2 H, s), 4.41 (2 H, d, J=6.3 Hz), 4.09 (2 H, br. s.), 3.93 (2 H, s), 2.52 (2 H, br. s.), 2.24 (3 H, s), 2.10 - 2.11 (3 H, m), 2.04 - 2.14 (4 H, m), 1.50 - 1.76 (2 H, m); LCMS (ES+, (M+H+water)+) m/z 593.5.

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2012/78834, 2012, A1 Location in patent: Page/Page column 88

32
cobalt(II) acetate hydrate [ No CAS ]
[ 10534-59-5 ]
[ 67455-94-1 ]
C₂₂H₁₈CoN₄O₆^(1-)*C₁₆H₃₆N⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With oxygen In N,N-dimethyl-formamide	2.3. Synthesis of 3 A 2.0 mmol of CoBr2*H2O, 2.0 mmol of H2bpb (1) and 4.0 mmol triethylamine were dissolved in 20 ml of DMF and stirred at RT and air for 20 min. Then 4.42 mmol of NEt4Br was added and the solution was stirred at RT and air an additional 12 h. DMF was removed in vacuo and the residue was dissolved in 30 ml of acetonitrile and filtered. Through adding 30 ml of diethyl ether to the solution and cooling down to 2 °C a brown precipitate was formed. After filtering, washing with diethyl ether and drying under vacuo the product was yielded as a brown powder (56%). The complex is air-stable in the solid state and can be stored for months without degradation.

Reference： [1]Adolph; Zevaco; Walter; Dinjus; Döring [Polyhedron, 2012, vol. 48, # 1, p. 92 - 98]

33
iron(II) acetate hydrate [ No CAS ]
[ 10534-59-5 ]
[ 67455-94-1 ]
C₂₂H₁₈FeN₄O₆^(1-)*C₁₆H₃₆N⁽¹⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With oxygen In N,N-dimethyl-formamide	2.3. Synthesis of 3 A 2.0 mmol of CoBr2*H2O, 2.0 mmol of H2bpb (1) and 4.0 mmol triethylamine were dissolved in 20 ml of DMF and stirred at RT and air for 20 min. Then 4.42 mmol of NEt4Br was added and the solution was stirred at RT and air an additional 12 h. DMF was removed in vacuo and the residue was dissolved in 30 ml of acetonitrile and filtered. Through adding 30 ml of diethyl ether to the solution and cooling down to 2 °C a brown precipitate was formed. After filtering, washing with diethyl ether and drying under vacuo the product was yielded as a brown powder (56%). The complex is air-stable in the solid state and can be stored for months without degradation.

Reference： [1]Adolph; Zevaco; Walter; Dinjus; Döring [Polyhedron, 2012, vol. 48, # 1, p. 92 - 98]

34
[ 1192651-49-2 ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: (1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With hydrogen; sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol Stage #2: tetrabutylammonium acetate In water; isopropyl alcohol	4.4a Example 4aTetrabutylammonium ([(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulphonyl]oxidanide was prepared as described below.(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (10 g, 36.2 mmol, 1 eq) was mixed with sulfur trioxide trimethylamine complex (6.07 g, 43.44 mmol, 1.2 eq), triethylamine (1.3 ml, 18 mmol, 0.25 eq), palladium on carbon (0.8 g, 10% palladium, 50% water), isopropanol (50 ml) and water (50 ml). This mixture was treated with hydrogen until the reaction was deemed to be complete. The catalyst was removed by filtration and washed with water (20 ml). The combined filtrates were washed with n-BuOAc (70 ml, 20 ml) before a solution of tetrabutylammonium acetate (54.5 mmol) in water (20 ml) was added. The product was extracted with dichloromethane (100 ml, 50 ml) and solvent swapped into 4-methyl-2-pentanone, before filtering, washing and drying to yield a white crystalline solid (16.9 g, 92%).1H NMR (400 MHz, CDCl3) δH 1.00 (12H, t), 1.45 (8H, m), 1.67 (9H, m), 1.87 (1H, m), 2.16 (1H, m), 2.37 (1H, dd), 2.87 (1H, d), 3.31 (9H, m), 3.91 (1H, d), 4.33 (1H, s), 5.79 (1H, s), 6.67 (1H, s).
89.6%	Stage #1: (1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen; sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol Stage #2: tetrabutylammonium acetate With acetic acid In water; isopropyl alcohol
85%	Stage #1: (1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With formic acid; palladium on activated charcoal; ammonium formate In isopropyl alcohol at 35℃; Stage #2: tetrabutylammonium acetate In water at 20℃; for 3h;	5 Example 5 Preparation of (Compound K) ([(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo)[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt: Isopropanol (9000 ml) was added to the reaction flask, and compound J (600.0 g), palladium on carbon (60.0 g), ammonium formate (68.7 g) and formic acid (200.5 g) were added.The reaction temperature was controlled at 30 ° C to 35 ° C for 2 to 3 hours, and the J reaction was completely detected by HPLC, followed by suction filtration and washing.Triethylamine (55.0 g) and trimethylamine trioxide (424.6 g) were added to the filtrate.The temperature is controlled at 30 ° C to 35 ° C, and the reaction is stirred for 3 to 4 hours.An aqueous solution of 35% tetrabutylammonium acetate (821.4 g) was added thereto, and the reaction was stirred at room temperature for 3 hours, and the reaction liquid was concentrated to 10 kg.Dichloromethane (3.6 kg X2) was added to the concentrated reaction mixture for 2 times. After phase separation, the organic phase was concentrated under vacuum at 40 to 50 ° C to give an oil.After adding 1800 ml of methyl isobutyl ketone, the mixture was subjected to crystallization, suction filtration, washing and drying to obtain 938.4 g of the title compound K. The yield was 85.0%, the purity was 99.7%, and the single impurity was <0.1%.

79.6%

Stage #1: (1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen; triethylamine In water; isopropyl alcohol Stage #2: tetrabutylammonium acetate In water

8 8, Preparation of (2S,5R)-1,6-diazacyclo[3.2.1]octane-2-carboxamide-7-oxo-6-sulfonate-tetrabutylammonium salt (9) Add (2S,5R)-6-benzyloxy-7-oxo-1,6-diazacyclo[3.2.1]octane-2-formamide (8) (10 g, 36.2 mmol) was added to a 250 ml single-mouth bottle, trimethylamine sulfur trioxide copolymer (6.07 g, 43.44mmol), triethylamine (1.3 ml,18 mmol), palladium on carbon (0.8 g, 10%), followed by isopropanol (50 ml) and water (50 ml), the reaction was completed to completion under hydrogen. The solid was removed by suction filtration, and the filtrate was added n-butyl acetate (70 ml, 20 ml), and the mixture was separated. Tetrabutylammonium acetate (16.4 g,54.5 mmol) was dissolved in water (20 ml) and slowly added dropwise to the obtained aqueous phase. After stirring until the reaction is completed, dichloromethane is added to separate the organic layer, which is dried over anhydrous sodium sulfate, and then filtered and evaporated to remove methylene chloride, then 4-methyl-2-pentanone (25 ml), and cooled to Stir at 0 °C, suction and dry to give a white solid (2S,5R)-1,6-diazacyclo[3.2.1]octane-2-carboxamide-7-oxo-6-sulfonyl-tetrabutyl The ammonium salt (9) (14.6 g, 79.6%).

Reference： [1]Current Patent Assignee: PFIZER INC - US2012/323010, 2012, A1 Location in patent: Page/Page column 24-25
[2]Wang, Tao; Du, Liang-Dong; Wan, Ding-Jian; Li, Xiang; Chen, Xin-Zhi; Wu, Guo-Feng [Organic Process Research and Development, 2018, vol. 22, # 12, p. 1738 - 1744]
[3]Current Patent Assignee: SHANGHAI FOSUN PHARMACEUTICAL (GROUP) CO., LTD. - CN107880042, 2018, A Location in patent: Paragraph 0048; 0049; 0052-0057
[4]Current Patent Assignee: ZHEJIANG MEDICINE CO., LTD. - CN108239089, 2018, A Location in patent: Paragraph 0065; 0066; 0067

35
(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile [ No CAS ]
[ 10534-59-5 ]
(2S,5R)-6-(sulfooxy)-7-oxo-1,6-diazabicyclo-[3.2.1]octane-2-carbonitrile tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide at 0 - 25℃; for 1h;	7 The debenzylated compound (IX) was dissolved in Ν,Ν'-Dimethyl formamide (30 ml) under argon atmosphere and the solution cooled to 0°C. DMF: SO3 (4.26 gm, 0.0278mol) was added to the cooled solution and the stirring continued further for 30 min at 0°C. The mixture was then allowed to warm to RT and stirred for 1 hour. TLC showed complete conversion of N-Hydroxy compound to product X. The solution containing the sulfate(X) was re-cooled to 0°C and a solution of Tetra butyl ammonium acetate (9 gm, 0.0301mol dissolved in 30ml water) was added to it. The reaction mixture was allowed to warm to 25°C and stirred for 1 hour. The volatiles were removed under reduced pressure and residue was co-evaporated with 2x50 ml Xylene to remove traces of Ν,Ν'-Dimethyl formamide. The residue was partitioned between a 1:1 mixture of water and dichloromethane (120ml). The aqueous layer was re-extracted with dichloromethane (30 ml). The combined organic extracts were washed with water (2x30ml), brine (30 ml). And dried over Na2SO4 and the solvent evaporated under reduced pressure to obtain the crude TBA sulfate (5.2 gm). Crude compound was triturated with hexane (2x30 ml) & dried on rotavapor under 4mmHg pressure to obtain the TBA salt (XI), 5.0 g, yield-44%. Mass: 246 (M-H) of sulfate M.W: 488, M.F: C23H44N4O5S.
52.5 g	Stage #1: (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonitrile With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at -5℃; for 1h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 1h;	1.4 Step 4: Synthesis of (25, 5R)-6-(sulfooxy)-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2- carbonitrile, tetrabutylammonium salt (VI): Step 4: Synthesis of (25, 5R)-6-(sulfooxy)-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2- carbonitrile, tetrabutylammonium salt (VI): To a solution of (25,5i?)-6-hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2- carbonitrile (20.66 g, 0.124 mol) in dimethylformamide (160 ml), sulfur trioxide dimethylformamide complex (22.8 g, 0.149 mol) was added in one portion under stirring at about -5°C. After 60 minutes of stirring, the completion of the reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (9: 1). To the resulting mixture was slowly added a solution of tetrabutylammomum acetate (48.6 g, 0.161 mol) in water (160 ml). After 1 hour of stirring, the solvent was evaporated under reduced pressure to obtain an oily residue. The oily residue was co-evaporated with xylene (2 x 200 ml), to yield a thick mass. This mass was partitioned between dichloromethane (320 ml) and water (320 ml). The organic layer was separated and the aqueous layer re-extracted with dichloromethane (160 ml). The combined organic extracts were washed with water (3 x 160 ml), dried (over anhydrous sodium sulfate) and the solvent was evaporated under reduced pressure at about 35°C. The residual oily mass was triturated with ether (3 xl60 ml), each time the ether layer was decanted and finally the residue was dried under reduced pressure, to obtain 52.5 g of (25, 5i?)-6-(sulfooxy)-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carbonitrile, tetrabutyl ammonium salt (VI) as an oil in 86% yield. Analysis: Mass: 246 (M-l) as free sulfonic acid; for Molecular Weight of 488 and Molecular Formula of C23H44N4O5S; 1H NMR (400 MHz, CDC13): δ 4.39 (brs, 1H), 4.34-4.32 (d, 1H), 3.41-3.33 (m, 2H), 3.27-3.22 (m, 8H), 2.28 (m, 2H), 1.89-1.84 (m, 2H), 1.67-1.59 (m, 8H), 1.47-1.37 (m, 8H), 1.00-0.96 (m, 12H); Purity as determined by HPLC: 95.24%.

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2013/38330, 2013, A1 Location in patent: Page/Page column 19
[2]Current Patent Assignee: WOCKHARDT LIMITED - WO2015/114595, 2015, A1 Location in patent: Page/Page column 13-14

36
[ 865255-93-2 ]
[ 10534-59-5 ]
iron(II) acetate [ No CAS ]
2C₁₆H₃₆N⁽¹⁺⁾*C₄₀H₈₀Fe₂N₁₄O₆^(2-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	Stage #1: bis[(N'-tert-butylureayl)-N-ethyl]-(N''-isopropylcarbamoyl-methyl)amine With potassium hydride In N,N-dimethyl acetamide Inert atmosphere; Stage #2: iron(II) acetate In N,N-dimethyl acetamide for 0.5h; Inert atmosphere; Stage #3: tetrabutylammonium acetate In N,N-dimethyl acetamide for 2h; Inert atmosphere;	[Bu₄N]₂[Fe(II)H₂2^iPr]₂ General procedure: A solution of H6buea (200 mg, 0.45 mmol) dissolved in 4 mL of anhydrous DMA was treated with solid KH (55 mg, 1.36 mmol) and stirred until gas evolution ceased. Fe(OAc)2 (79 mg, 0.45 mmol) was added to the pale yellow solution, and stirring was continued for 30 min. The resulting amber filtrate was treated with [Bu4N][OAc] (140 mg, 0.45 mmol) and stirred for 2 h, resulting in the precipitation of a white solid (305 mg) that was filtered, washed twice with Et2O, and dried under vacuum. The white solid was stirred in CH3CN for 1 h and filtered to remove KOAc (105 mg, 96%). The light yellow filtrate was concentrated to half its original volume and the slow addition of Et2O resulted in the formation of a white solid, which was then filtered, washed with Et2O, and dried under vacuum to afford 150 mg (47%) of the desired salt. [Bu4N]2[Fe(II)H22iPr]2 was prepared following a similar procedure to that of [Bu4N]2[Fe(II)H3buea]2 with H52iPr (150 mg, 0.37 mmol), KH (45 mg, 1.12 mmol), Fe(OAc)2 (66 mg, 0.37 mmol), and [Bu4N][OAc] (113 mg, 0.37 mmol). The amount of KOAc obtained was 105 mg (96% for 3 equiv) and 100 mg (42%) of [Bu4N]2[FeIIH22iPr] was isolated. FTIR (Nujol, cm-1) ν(NH) 3332, ν(CO) 1661, 1590, 1561, 1520. Repeated attempts to obtain a satisfactory elemental analysis were unsuccessful.

Reference： [1]Lacy, David C.; Mukherjee, Jhumpa; Lucas, Robie L.; Day, Victor W.; Borovik [Polyhedron, 2013, vol. 52, p. 261 - 267]

37
[ 222613-94-7 ]
[ 10534-59-5 ]
iron(II) acetate [ No CAS ]
[Bu₄N]₂[Fe^IIH₃buea]₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	Stage #1: N,N',N''-(nitrilotri-2,1-ethanediyl)tris[N'-tertbutylurea] With potassium hydride In N,N-dimethyl acetamide Inert atmosphere; Stage #2: iron(II) acetate In N,N-dimethyl acetamide for 0.5h; Inert atmosphere; Stage #3: tetrabutylammonium acetate In N,N-dimethyl acetamide for 2h; Inert atmosphere;	[Bu₄N]₂[Fe(II)H₃buea]₂. General procedure: A solution of H6buea (200 mg, 0.45 mmol) dissolved in 4 mL of anhydrous DMA was treated with solid KH (55 mg, 1.36 mmol) and stirred until gas evolution ceased. Fe(OAc)2 (79 mg, 0.45 mmol) was added to the pale yellow solution, and stirring was continued for 30 min. The resulting amber filtrate was treated with [Bu4N][OAc] (140 mg, 0.45 mmol) and stirred for 2 h, resulting in the precipitation of a white solid (305 mg) that was filtered, washed twice with Et2O, and dried under vacuum. The white solid was stirred in CH3CN for 1 h and filtered to remove KOAc (105 mg, 96%). The light yellow filtrate was concentrated to half its original volume and the slow addition of Et2O resulted in the formation of a white solid, which was then filtered, washed with Et2O, and dried under vacuum to afford 150 mg (47%) of the desired salt. Anal. Calc. for [Bu4N]2[FeIIH3buea]2, C74H156Fe2N16O6: C, 60.14; H, 10.64; N, 15.16. Found: C, 61.19; H, 10.89; N, 15.68%. FTIR (Nujol, cm-1) ν(NH) 3335, ν(CO) 1663, 1592, 1571, 1556.

Reference： [1]Lacy, David C.; Mukherjee, Jhumpa; Lucas, Robie L.; Day, Victor W.; Borovik [Polyhedron, 2013, vol. 52, p. 261 - 267]

38
[ 3153-26-2 ]
[ 10534-59-5 ]
C₁₆H₃₆N⁽¹⁺⁾*5V⁽⁵⁺⁾*13O^(2-)*C₂H₃O₂^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In acetonitrile at 20℃; for 6h;	4.1. Synthesis of polyoxovanadates General procedure: Preparation of four different solutions of tetradecavanadates, VxOyALz (A = Cl- or CH3CO2-, L = (C2H5)4N+ or (C4H9)4N+), was carried out according to a modified literature procedure [31]. All chemicals were purchased from Sigma-Aldrich and used as received. Briefly, 1.5 mmol of vanadyl acetylacetonate [VO(acac)2] and 0.6 mmol of either tetraethylammonium chloride [(C2H5)4NCl], tetrabutylammonium chloride [(C4H9)4NCl], tetraethylammonium acetate [(C2H5)4N(CH3CO2)] or tetrabutylammonium acetate [(C4H9)4N(CH3CO2)] were dissolved in 50 mL of acetonitrile. 0.8 mmol of triethyl amine was then added to the initial mixtures while stirring constantly at room temperature. Following 6 h of reaction, an Oakton 10 series pH meter (calibrated using buffers of pH 4, 7 and 10 at room temperature) was used to determine the pH of the resulting brown-colored solutions. The product mixtures were de-solvated under reduced pressure using a VWR1400E vacuum oven. Recrystallization was carried out in approximately 3 mL of N,N-dimethylformamide (N,N-DMF) by heating the solution to the boiling temperature (153 °C) for 10 min. Any remaining N,N-DMF was then evaporated in vacuum to obtain pure dry crystals of polyoxovanadates. A small quantity of crystals was dissolved in acetonitrile to prepare concentrated stock solutions. These stock solutions were diluted further by factors of ten or one hundred in acetonitrile prior to analysis by ESI-MS.

Reference： [1]Johnson, Grant E.; Al Hasan, Naila M.; Laskin, Julia [International Journal of Mass Spectrometry, 2013, vol. 354-355, p. 333 - 341]

39
[ 3153-26-2 ]
[ 10534-59-5 ]
C₁₆H₃₆N⁽¹⁺⁾*7V⁽⁵⁺⁾*18O^(2-)*C₂H₃O₂^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In acetonitrile at 20℃; for 6h;	4.1. Synthesis of polyoxovanadates General procedure: Preparation of four different solutions of tetradecavanadates, VxOyALz (A = Cl- or CH3CO2-, L = (C2H5)4N+ or (C4H9)4N+), was carried out according to a modified literature procedure [31]. All chemicals were purchased from Sigma-Aldrich and used as received. Briefly, 1.5 mmol of vanadyl acetylacetonate [VO(acac)2] and 0.6 mmol of either tetraethylammonium chloride [(C2H5)4NCl], tetrabutylammonium chloride [(C4H9)4NCl], tetraethylammonium acetate [(C2H5)4N(CH3CO2)] or tetrabutylammonium acetate [(C4H9)4N(CH3CO2)] were dissolved in 50 mL of acetonitrile. 0.8 mmol of triethyl amine was then added to the initial mixtures while stirring constantly at room temperature. Following 6 h of reaction, an Oakton 10 series pH meter (calibrated using buffers of pH 4, 7 and 10 at room temperature) was used to determine the pH of the resulting brown-colored solutions. The product mixtures were de-solvated under reduced pressure using a VWR1400E vacuum oven. Recrystallization was carried out in approximately 3 mL of N,N-dimethylformamide (N,N-DMF) by heating the solution to the boiling temperature (153 °C) for 10 min. Any remaining N,N-DMF was then evaporated in vacuum to obtain pure dry crystals of polyoxovanadates. A small quantity of crystals was dissolved in acetonitrile to prepare concentrated stock solutions. These stock solutions were diluted further by factors of ten or one hundred in acetonitrile prior to analysis by ESI-MS.

Reference： [1]Johnson, Grant E.; Al Hasan, Naila M.; Laskin, Julia [International Journal of Mass Spectrometry, 2013, vol. 354-355, p. 333 - 341]

40
[ 1552316-78-5 ]
[ 10534-59-5 ]
[ 1552314-62-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	In acetonitrile at 75℃; for 0.666667h; Inert atmosphere;	124.3 The chloromethyl (9S, HE, 13S)-13,16-dimethyl-6-oxo-3,7,14,17,23- pentaazapentacyclo[13.6.2.1~2,5~.0~4,9~.0~18,22~]tetracosa- l(22),2(24),4,l l,15,17,18,20,22-nonaene-7-carboxylate from Step 2 (0.053 g, 0.117 mmol) and tetrabutylammonium acetate (Aldrich; 0.070 g, 0.232 mmol) were suspended in dry ACN (5 mL) under N2 and heated in a 75 0 C oil bath. After stirring for 40 minutes the mixture was cooled and evaporated to dryness under reduced pressure. Purification using silica chromatography (DCM to EtOAc gradient) gave the desired macrocycle contaminated with some tetrabutylammonium salts. The material was dissolved in DCM (10 mL) and washed with water (2 x 10 mL). The organic was dried with MgS04 and evaporated to dryness under reduced pressure to give (acetyloxy)methyl (9S, 1 IE, 13S)- 13,16-dimethyl-6-oxo-3,7,l 4, 17,23-pentaazapenta- cyclo[13.6.2.1~2,5~.0~4,9~.0~18,22~]tetracosa-l(22),2(24),4,l l, 15, 17,18,20,22- nonaene-7-carboxylate (0.0468 g, 0.098 mmol, 84 % yield) : FontWeight="Bold" FontSize="10" H NMR (400 MHz, CDC ) d ppm 13.52 (1 H, br. s.), 7.86 - 7.93 (1 H, m), 7.64 (1 H, d, J=8.0 Hz), 7.37 (1 H, t, J=7.8 Hz), 7.04 (1 H, d, J=2.2 Hz), 5.93 (2 H, q, J=5.7 Hz), 5.78 - 5.84 (2 H, m), 4.72 (1 H, s), 4.51 (1 H, dd, J=12.3, 4.7 Hz), 4.20 (1 H, quin, J=6.2 Hz), 3.40 (1 H, t, J=12.5 Hz), 3.22 - 3.32 (1 H, m), 2.50 - 2.63 (4 H, m), 2.06 - 2.19 (4 H, m), 1.51 (3 H, d, J=6.8 Hz), m/z (ESI, +ve) 476.0 (M+H)+.

Reference： [1]Current Patent Assignee: AMGEN INC - WO2014/22752, 2014, A1 Location in patent: Page/Page column 237; 238

41
[ 1452466-55-5 ]
[ 10534-59-5 ]
[ 1572989-96-8 ]

Yield	Reaction Conditions	Operation in experiment
610 mg	Stage #1: 2-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl)aminooxymethyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 2h;	1.2 Step-2: Preparation of tetrabutylammonium salt of (2,S',5ii)-2-[(6-sulfooxy-7-oxo-l,6- diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2,S')-pyrrolidine-l- carboxylic acid tert-butyl ester Step-2: Preparation of tetrabutylammonium salt of (2,S',5ii)-2-[(6-sulfooxy-7-oxo-l,6- diaza-bicyclo[3.2.1]octane-2-carbonyl)-methyloxycarbamoyl]-(2,S')-pyrrolidine-l- carboxylic acid tert-butyl ester: A solution of the Benzyl compound (2.1g, mmol) in 1: 1 mixture of DMF: DCM (5ml), was hydrogenated over 10% Pd/C (125mg) over 1 atmosphere of Hydrogen balloon. After stirring for 4 hours the reaction mixture was filtered over celite. The filtrate was concentrated under reduced pressure and the residue obtained was dissolved in fresh DMF (2.5ml) and cooled to 10°C.SO3.DMF complex (193mg, 12.6mmol) was added and the reaction mixture was allowed to warm to RT. After stirring RM at RT for 1.5 hours, TBAA (379mg, 12.6mmol) in water (1.25ml) was added to the reaction mixture and stirring continued further for 2hours. The volatiles were removed by high vacuum distillation and the residue co-evaporated with xylene (2X25ml) to remove traces of DMF. The residue obtained was diluted with water (20ml) and extracted with DCM (3X20ml). The combined DCM layer was washed with water (2X20ml). The DCM layer was dried and the solvent evaporated under reduced pressure. The crude residue was triturated with Diethyl ether (3X25ml) to obtain the product as a white solid, 610mg, 82% yield. Analysis: Mass: 463.4 (M-H) for MW-705.96 and M.F- C33H63N509 S. XH NMR: Solvent(CDCl3): 10.2 (s, 1H), 4.35 (s, 1H), 4.14 (s, 1H), 3.91-3.92 (d, 2H), 3.74 (m, 1H), 3.36-3.27 (m, 10H), 2.96-2.88 (dd, 2H), 2.31-2.26 (m, 2H), 2.19-1.98 (m, 2H), 1.95-1.70 (m, 4H), 1.68-1.62 (p, 8H), 1.49-1.40 (m, 17H), 1.02-0.98 (t, 12H) .
102 g	Stage #1: 2-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbonyl)aminooxymethyl]-(2S)-pyrrolidine-1-carboxylic acid tert-butyl ester With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 2.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide at 20℃; for 2h;	2.3 Step 3: Synthesis of tert-butyl(25)-2-[([25,5R)-6-(sulfooxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]methyl}pyyrolidine-l-carboxylate, tetra butyl ammonium salt (VI): Step 3: Synthesis of tert-butyl(25)-2-[([25,5R)-6-(sulfooxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]methyl}pyyrolidine-l-carboxylate, tetra butyl ammonium salt (VI): To solution of ieri-butyl(25)-2-{ [({ [25,5i?)-6-hydroxy7-oxo-l,6-diazabicylco [3.2.1]oct-2-yl]carbonyl}amino)oxy]methyl}pyyrolidine-l-carboxylate (V, 68.8 g, 0.178 mol) in dimethylformamide, (345 ml) was added sulfur trioxide dimethylformamide complex (30 g, 0.196 mol) under stirring at temperature of about 10 °C. The reaction mass was stirred at the same temperature for 30 minutes and then allowed to warm to room temperature. After 2 hours solution of tetra butyl ammonium acetate (59.09 g, 0.196 mol) in water (178 ml) was added to the reaction mixture under stirring. After 2 hours, the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2x140 ml) to obtain thick mass. This mass was partitioned between dichloromethane (690 ml) and water (690 ml). The organic layer was separated and the aqueous layer re-extracted with dichloromethane (345 ml). The combined organic extracts were washed with water (3x345 ml) and dried over anhydrous sodium sulfate.The solvent was evaporated under reduced pressure and the resulting oily mass was triturated with ether (3x140 ml), each time the ether layer was decanted and finally the residue was concentrated under reduced pressure to obtain 102 g of ieri-butyl(25)-2- { [({ [25,5i?)-6-(sulfooxy)-7-oxo- l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]methyl}pyyrolidine- l-carboxylate, tetrabutyl ammonium salt (VI) as fluffy material.Analysis:Mass: 463.4 (M- l without TBA), for Molecular Weight of 705.96 and Molecular Formula of C33H63N5O9 S;1H NMR (400 MHz, CDCI3): δ 10.2 (s, 1H), 4.35 (s, 1H), 4.14 (s, 1H), 3.91 -3.92 (d, 2H), 3.74 (m, 1H), 3.36-3.27 (m, 10H), 2.96-2.88 (dd, 2H), 2.31-2.26 (m, 2H), 2.19- 1.98 (m, 2H), 1.95-1.70 (m, 4H), 1.68- 1.62 (p, 8H), 1.49- 1.40 (m, 17H), 1.02-0.98 (t, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2014/33560, 2014, A1 Location in patent: Page/Page column 36-37
[2]Current Patent Assignee: WOCKHARDT LIMITED - WO2015/79329, 2015, A2 Location in patent: Page/Page column 8; 19; 20

42
C₇₈H₇₀N₄O₆ [ No CAS ]
[ 10534-59-5 ]
[ 58520-03-9 ]
C₉₄H₈₆N₆O₆*C₂H₃O₂^(1-)*C₁₆H₃₆N⁽¹⁺⁾ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 5464 - 5468

43
C₇₈H₇₀N₄O₆ [ No CAS ]
[ 10534-59-5 ]
[ 138517-66-5 ]
C₉₄H₈₂N₆O₄*C₂H₃O₂^(1-)*C₁₆H₃₆N⁽¹⁺⁾ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 5464 - 5468

44
tert-butyl 2-((6S)-6-(chloromethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate [ No CAS ]
[ 10534-59-5 ]
[ 154026-95-6 ]
tert-butyl 2-((4S,6S)-6-(acetoxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one; at 25 - 85℃; for 24h;	To a solution of tert-b tyl 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-l,3-dioxan-4- yl)acetate (10 g, 60% de) in NMP (300 mL) was added tetra butyl ammonium acetate (30 g) at 25C. Resulting reaction mixture was heated to 85C and stirred for 24 h. After cooling to room temperature, water (450 mL) was added and then extracted with n- heptane (3 X 150 mL). To the combined organic layer was added activated charcoal (1 g) and stirred for 5 h, filtered off the activated charcoal and filtrate was concentrated to obtained product as off white solid material (7.2g, 65% de).

Reference： [1]Patent: WO2014/203045,2014,A1 .Location in patent: Page/Page column 44

45
[ 1623-88-7 ]
[ 10534-59-5 ]
[ 10551-58-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	In acetonitrile at 20℃; for 0.0833333h;	1 Example 1 Example 1 In a round flask, 2 mL of methyl cyanide (acetonitrile) as an organic solvent was introduced, 0.145 g (1 mmol) of 5-chloromethylfurfural (CMF, compound I) was dissolved in the organic solvent, 0.302 g (1 mmol) of tetrabutylammonium acetate was added to the solution, and then the mixed solution was reacted at normal pressure and room temperature for 5 minutes. After the reaction, the reaction product was extracted by the addition of a small amount of water (5 mL) and ethyl acetate (added twice by 20 mL) to obtain an organic layer. The obtained organic layer was concentrated under reduced pressure to obtain light yellow liquid 5-acetoxymethylfurfural (AcHMF, compound II). The yield thereof is 97%. It was ascertained by 1H-NMR that the light yellow liquid is a target material. Analysis data is as follows. AcHMF: 1H NMR (400 MHz, CDCl3) 9.65 (s, 1H), 7.25 (d, J=3.6, 1H), 6.62 (d, J=3.6, 1H), 5.13 (s, 2H), 2.12 (s, 3H)
96%	In acetonitrile at 20℃;

Reference： [1]Current Patent Assignee: KOREA INSTITUTE OF INDUSTRIAL TECHNOLOGY; SEOUL NATIONAL UNIVERSITY - US2015/51413, 2015, A1 Location in patent: Paragraph 0061; 0062; 0063
[2]Kang, Eun-Sil; Hong, Yeon-Woo; Chae, Da Won; Kim, Bora; Kim, Baekjin; Kim, Yong Jin; Cho, Jin Ku; Kim, Young Gyu [ChemSusChem, 2015, vol. 8, # 7, p. 1179 - 1188]

46
benzyl (2-((((2,3-bis(trifluoromethyl)sulfonyl)oxy)-4,6-di-O-benzoyl-β-D galactopyranosyl)oxy)ethyl)carbamate [ No CAS ]
[ 10534-59-5 ]
benzyl (2-((2,3-di-O-acetyl-4,6-di-O-benzoyl-β-D mannopyranosyl)oxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.5%	In N,N-dimethyl-formamide; toluene at 20℃;	60.C Step C: To a solution of benzyl (2-((((3,5-bis(trifluoromethyl)sulfonyl)oxy)-4,6-di-O-benzoyl-β-D galactopyranosyl)oxy)ethyl)carbamate (16.9 g, 20.37 mmol) in anhydrous toluene (100 mL), was added a solution of tetra butylammonium acetate (25 g, 82.9 mmol) in a mixture of toluene (150 mL) and DMF (4 mL) was added and the resulting mixture stirred at room temperature overnight. Diluted with of CH2Cl2 (30 mL) and washed with sat. NaCl (2*100 mL), dried over MgSO4, filtered and evaporated. The residue was purified by silica gel column chromatography (Teledyne Isco: 330 g) eluent: 0-50% EtOAc/Hexane (10cv) then 50% EtOAc/Hexane (5cv) to give the title compound (8 g, 60.5%). 1H NMR (CDCl3) δ 8.10 (2H, m), 7.98 (2H, dd, J=8.1 and 1.4 Hz), 7.61 (2H, m), 7.48 (2H, t, J=7.8 Hz), 7.46 (2H, t, J=7.7 Hz), 7.37 (4H, m), 7.33 (1H, m), 5.70 (1H, d, J=3.3 Hz), 5.61 (1H, t, J=10.0 Hz), 5.29 (1H, dd, J=10.0 and 3.3 Hz), 5.26 (1H, m), 5.10 (2H, s), 4.79 (1H, s), 4.64 (1H, dd, J=12.1 and 2.7 Hz), 4.47 (1H, dd, J=12.1 and 5.8 Hz), 3.94 (2H, m), 3.74 (1H, m), 3.48 (1H, m), 3.37 (1H, m), 2.15 (3H, s), 2.00 (3H, s).

Reference： [1]Current Patent Assignee: PISSARNITSKI DIMITRI; MERCK & CO INC - US2015/105317, 2015, A1 Location in patent: Paragraph 0606

47
[ 1452465-84-7 ]
[ 10534-59-5 ]
(3S)-3-[([(2S,5R)-7-oxo-6-sulphooxy-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)oxy]pyrrolidin-1-carboxylic acid tert-butyl ester tetrabutylammonium [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: (3S)-3-[([(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)oxy]pyrrolidin-1-carboxylic acid tert-butyl ester With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 2.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 2h;	2.3 Step 3: Preparation of tert-butyl-(35)-3-[([25,5R)-6-(sulfooxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]pyrrolidine-l-carboxylate, tetrabutyl ammonium salt (VI) Step 3: Preparation of tert-butyl-(35)-3-[([25,5R)-6-(sulfooxy)-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]pyrrolidine-l-carboxylate, tetrabutyl ammonium salt (VI): To a stirred solution of ieri-butyl(35)-3-[({ [25,5i?)-6-hydroxy-7-oxo-l,6- diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy]pyrrolidine-l-carboxylate (V) (8.04 g, 0.0217 mol) in dimethylformamide (50 ml), was added sulfur trioxide dimethyl formamide complex (3.98 g, 0.0260 mol) in one portion, at about 10°C. The stirring was continued further for 30 minute and then the reaction mixture was allowed to warm to room temperature. After 2 hour, a solution of tetrabutylammonium acetate (7.83 g, 0.0260 mol) in water (25.8 ml) was added to the resulting reaction mass under stirring. After additional 2 hour of stirring, the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2 x 20 ml) to obtain thick mass. This mass was partitioned between dichloromethane (100 ml) and water (100 ml). The organic layer was separated and the aqueous layer re-extracted with dichloromethane (50 ml). The combined organic extracts were washed with water (3 x 50 ml), dried over anhydrous sodium sulphate and the solvent evaporated under reduced pressure. The residual oily mass was triturated with ether (3 x 50 ml), each time the ether layer was decanted and finally the residue was concentrated under reduced pressure to obtain 11.3 g of tert-butyl(3S)-3-[({ [2S,5R)-6- (sulfooxy)-7-oxo-l,6-diazabicylco[3.2.1]oct-2-yl]carbonyl}amino)oxy] pyrrolidine- 1- carboxylate, tetrabutylammonium salt (VI), as a white foam, in 75 % yield. Analysis: Mass: 449.3 (M-l, without TBA); for Molecular weight of 691.94 and Molecular formula of C32H61N5O9S; and 1H NMR (400MHz, CDC13): 59.14-9.10 (d, 1H), 4.63 (s, 1H), 4.35 (s, 1H), 3.94- 3.92 (d, 1H), 3.66-3.35 (m, 5H), 3.29-3.27 (m, 8H), 2.83-2.80 (d, 1H), 2.35-2.17 (m, 3H), 1.98-1.87 (m, 2H), 1.73 (m, 1H), 1.70-1.62 (m, 8H), 1.49-1.40 (m, 17H), 1.02-0.99 (t, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2015/110886, 2015, A1 Location in patent: Page/Page column 18-19

48
[ 1044740-40-0 ]
[ 10534-59-5 ]
(2S,3R)-N-benzyl-3-acetoxy-2-(trifluoromethyl)piperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: (R)-2-[(S)-1-benzyl-2-pyrrolidinyl]-1,1,1-trifluoro-2-ethanol With trifluoromethylsulfonic anhydride; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at -15℃; for 0.0833333h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In dichloromethane at -15℃; for 1.5h; Inert atmosphere; diastereoselective reaction;

Reference： [1]Rioton, Sarah; Orliac, Aurélie; Antoun, Zeina; Bidault, Roselyne; Gomez Pardo, Domingo; Cossy, Janine [Organic Letters, 2015, vol. 17, # 12, p. 2916 - 2919]

49
2'-chloro-4'-nitrophenyl 2-O-benzoyl-4,6-benzylidene-3-O-triflyl-β-D-glucopyranoside [ No CAS ]
[ 10534-59-5 ]
2'-chloro-4'-nitrophenyl 3-O-acetyl-2-O-benzoyl-4,6-benzylidene-β-D-allopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	In N,N-dimethyl-formamide at 0℃; for 0.25h;	4.5.23 2′-Chloro-4′-nitrophenyl 3-O-acetyl-2-O-benzoyl-4,6-benzylidene-β-D-allopyranoside (20) The synthesis was performed according to a general protocol for related compounds [36]. Tetrabutylammonium acetate (1.92g, 6.383mmol, 3.0equiv.) was added to a solution of 19 (1.40g, 2.128mmol) in 15mL dry DMF at 0°C. After 15min, the solution was poured into 50mL of ice-water. The resulting mixture was extracted with 100mL ethyl acetate three times each. The combined organic layer was washed with 50mL water, 40mL brine, separated, and dried over anhydrous sodium sulfate. After filtration and concentration, a residue was obtained that was purified by column chromatography over silica gel column (hexane/ethyl acetate=8/1-6/1, v/v) to give compound 20 (1.10g, 1.941mmol, 91%) as a colorless foam; Rf 0.33 (SiO2, cyclohexane/ethyl acetate=4/1, v/v); δH (CD2Cl2) 8.24 (d, 2.8, 1H), 8.17 (dd, 9.0, 2.8, 1H), 7.92-7.98 (m, 2H), 7.56-7.64 (m, 1H), 7.41-7.48 (m, 4H), 7.34-7.40 (m, 4H), 6.00 (t, 2.9, 1H), 5.68 (d, 8.3, 1H), 5.63 (s, 1H), 5.55 (dd, 8.2, 3.1, 1H), 4.49 (dd, 10.5, 5.0, 1H), 4.27 (td, 9.9, 5.1, 1H), 4.00 (dd, 9.5, 2.5, 1H), 3.89 (t, 10.3, 1H), 2.16 (s, 3H); δC (CD2Cl2) 170.0, 165.2, 158.1, 143.6, 137.4, 134.1, 130.2, 129.7, 129.7, 129.1, 128.8, 126.7, 126.6, 125.2, 124.2, 116.8, 102.3, 98.9, 76.5, 70.3, 69.3, 68.7, 65.6, 21.1; HRMS (ESI-TOF+) m/z calcd. for C28H25ClNO10 [M+H]+ 570.1167; found 570.1152.

Reference： [1]Striegler, Susanne; Fan, Qiu-Hua; Rath, Nigam P. [Journal of Catalysis, 2016, vol. 338, p. 349 - 364]

50
[ 10534-59-5 ]
potassim 4-fluorophenyltrifluoroborate [ No CAS ]
[ 405-51-6 ]

Yield	Reaction Conditions	Operation in experiment
65%	With copper(II) bis(trifluoromethanesulfonate); In acetonitrile; at 25℃; for 16h;Sealed tube;	General procedure: Potassium (4-fluorophenyl)trifluoroborate (1) (101 mg, 0.5 mmol, 1 equiv) or potassium(4-biphenyl)trifluoroborate (130 mg, 0.5 mmol, 1 equiv), Cu(OTf)2 (722 mg, 2 mmol, 4equiv) and tetraalkylammonium or alkali salt (2 mmol, 4 equiv) were weighed into a 20mL vial equipped with a magnetic stir bar. CH3CN (6 mL) was added, and the vial wassealed with a Teflon-lined cap. The reaction mixture was allowed to stir at roomtemperature for 16 h. For products that were isolated, the reactions were diluted withdiethyl ether or pentane (10 mL), and this solution was washed with water (3 x 10 mL).The organic layer was dried over MgSO4, filtered, and concentrated under vacuum. Theproducts were purified by column chromatography on silica gel. For product yieldsdetermined by 19F NMR spectroscopy, the crude reaction mixture was diluted withCH3CN, 1,3,5-trifluorobenzene was added as an internal standard, and the reaction wasanalyzed by 19F NMR spectroscopy.

Reference： [1]Synlett,2016,vol. 27,p. 2279 - 2284

51
3-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}benzene [ No CAS ]
[ 10534-59-5 ]
3-{3-[(2S,5R)-6-(sulfooxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl]ureido}benzene tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: 3-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}benzene With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 1h;	1.3 Step 3: Preparation of tetrabutylammonium salt of 3-{3-[(25,5R)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-benzene Step 3: Preparation of tetrabutylammonium salt of 3-{3-[(25,5R)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-benzene: To a stirred solution of 3-{3-[(2S,5R)-(6- hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]-ureido}-benzene (0.46 g, 0.0015 mol) in dimethylformamaide (4.5 ml) was added dimethylformamide- sulphur trioxide complex (0.256 g, 0.0016 mol) in one portion, at about 10°C under stirring. The reaction mass was stirred at the same temperature for about 30 minutes and allowed to warm to room temperature. After 1 hour, a solution of tetrabutylammonium acetate (0.501 g, 0.0016 mol) in water (2 ml) was added slowly to the resulting reaction mass under stirring. After 1 hour, the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2 x 10 ml) to obtain thick mass. This mass was partitioned between dichloromethane (10 ml) and water (10 ml). The combined organic extracts were washed with water (3x10 ml) and dried over anhydrous sodium sulphate.The solvent was evaporated under reduced pressure and the resulting oily mass was triturated with ether (3x10 ml) (each time the ether layer was decanted). Finally, the residue was concentrated under reduced pressure to obtain the 0.4 g of the titled product as white foam in 44% yield.Analysis: Mass: 383.5.4 (M- l) as free acid; for Molecular Weight: 625.82 and Molecular Formula:

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2016/116788, 2016, A1 Location in patent: Page/Page column 28; 29

52
3-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}pyridine [ No CAS ]
[ 10534-59-5 ]
3-{3-[(2S,5R)-6-(sulfooxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl]ureido}pyridine tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	Stage #1: 3-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}pyridine With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 1h;	2.3 Step 3: Preparation of tetrabutylammonium salt of 3-{3-[(25,5/?)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-pyridine Step 3: Preparation of tetrabutylammonium salt of 3-{3-[(25,5/?)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-pyridine: To a stirred solution of 3-{3-[(25,57?)-(6- hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]-ureido}-pyridine (0.385 g, 0.0012 mol) in dimethylformamide (4.5 ml) was added dimethylformamide sulphur trioxide complex (0.256 g, 0.0016 mol) in one portion, at about 10°C. The reaction mass was stirred at the same temperature for 30 minutes and allowed to warm to room temperature. After 1 hour, to the resulting reaction mass was added slowly a solution of tetra butyl ammonium acetate (0.501 g, 0.0016 mol) in water (2 ml) under stirring. After 1 hour the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2x10 ml) to obtain thick mass. This mass was partitioned between dichloromethane (10 ml) and water (10 ml). The combined organic extracts were washed with water (3x10 ml) and dried over anhydrous sodium sulphate.The solvent was evaporated under reduced pressure and the resulting oily mass was triturated with ether (3x10 ml), each time the ether layer was decanted and finally the residue was dried under reduced pressure to obtain 0.4 g of the titled product as white foam in 44% yield.Analysis:384.3 (M- l) as free acid; for Molecular Weight: 626.8 and Molecular Formula:

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2016/116788, 2016, A1 Location in patent: Page/Page column 30

53
4-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
[ 10534-59-5 ]
4-{3-[(2S,5R)-6-(sulfooxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl]ureido}piperidine-1-carboxylic acid tert-butyl ester tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	Stage #1: 4-{3-[(2S,5R)-(6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)]ureido}piperidine-1-carboxylic acid tert-butyl ester With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; Stage #2: tetrabutylammonium acetate In dichloromethane; N,N-dimethyl-formamide for 1h;	3.3 Step 3: Preparation of tetrabutylammonium salt of 4-{3-[(25,5/f)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-piperidine-l-carboxylic acid tert-butyl ester Step 3: Preparation of tetrabutylammonium salt of 4-{3-[(25,5/f)-6-(sulfooxy)-7-oxo-l,6-diaza- bicyclo[3.2.1]octane-2-carbonyl]-ureido}-piperidine-l-carboxylic acid tert-butyl ester: To a stirred solution of 4-{ 3-[(2S,5R)-(6-hydroxy-7-oxo-l,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-ureido] }- piperidine-l-carboxylic acid tert-butyl ester (0.41 g, 0.0009 mol) in dimethylformamide (4.1 ml), at 10°C, was added dimethylformamide sulfur trioxide complex (0.183 g, 0.0019 mol) in one portion. The reaction mass was stirred at the same temperature for about 30 minutes and then allowed to warm to room temperature. After 1 hour, to the resulting reaction mixture was added slowly a solution of tetrabutylammonium acetate (0.359 g, 0.0019 mol) in dichloromethane (2 ml) under stirring. After 1 hour, the solvent from the reaction mixture was evaporated under reduced pressure to yield an oily residue. The oily mass was co-evaporated with xylene (2x10ml) to obtain a thick mass. This mass was partitioned between dichloromethane (10 ml) and water (10 ml). The combined organic extracts were washed with water (3xl0ml) and dried over anhydrous sodium sulphate.The solvent was evaporated under reduced pressure and the resulting oily mass was triturated with ether (3x10 ml), each time the ether layer was decanted and finally the residue was concentrated under reduced pressure to obtain 0.260 g of the titled product as white foam in 35% yield.Analysis:Mass: 490.4 (M-l) as free acid; for Molecular Weight: 732.9, Molecular Formula: C34H64N6O9S .

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2016/116788, 2016, A1 Location in patent: Page/Page column 31

54
(2S,5R)-N-[(3R)-1-(tert-butoxycarbonyl)piperidine-3-carbonyl]-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
(2S,5R)-N-[(3R)-1-(tert-butoxycarbonyl)piperidine-3-carbonyl]-6-(sulfooxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: (2S,5R)-N-[(3R)-1-(tert-butoxycarbonyl)piperidine-3-carbonyl]-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 20℃; for 1.5h; Stage #2: tetrabutylammonium acetate In dichloromethane for 1h;	6.4 Step 4: Preparation of tetrabutylammonium salt of (2S,5R)-N-[(3/?)-l-(ferf-butoxycarbonyl) piperidine-3-carbonyl]-6-(sulfooxy)-7-oxo-l,6-diazabicyclo[3.2.1]octane-2-carboxamide Step 4: Preparation of tetrabutylammonium salt of (2S,5R)-N-[(3/?)-l-(ferf-butoxycarbonyl) piperidine-3-carbonyl]-6-(sulfooxy)-7-oxo-l,6-diazabicyclo[3.2.1]octane-2-carboxamide: To a stirred solution of (2S,5 ?)-N-[(3^)-l-(ieri-butoxycarbonyl)piperidine-3-carbonyl]-6-hydroxy-7-oxo- l,6-diazabicyclo[3.2.1]octane-2-carboxamide (0.480 g, 0.0012mol) in dimethylformamide (4.8 ml), at about 10°C, was added dimethylformamide sulphur trioxide complex (0.207 g, 0.0013mol) in one portion. The reaction mass was stirred at the same temperature for 30 minutes and allowed to warm to room temperature. After 1 hour of stirring, to the reaction mixture was added, slowly, a solution of tetrabutylammonium acetate (0.408 g, 0.0013 mol) in dichloro methane (2 ml) and the stirring continued further. After 1 hour, the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2x10 ml) resulting in a thick mass. This mass was partitioned between dichloromethane (10 ml) and water (10 ml) for three times. The combined organic extracts were washed with water (3x10 ml), dried (over anhydrous sodium sulphate) and the solvent was evaporated under reduced pressure. The resulting oily mass was triturated with ether (3x10 ml), each time the ether layer was decanted and finally the residue was concentrated under reduced pressure to obtain 0.7 g of the titled product as white foam in 80% yield.Analysis:475.4 (M-l) as free acid; for Molecular Weight: 717.95 and Molecular Formula:

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2016/116788, 2016, A1 Location in patent: Page/Page column 33; 34

55
benzyl (2-((((2,3-bis(trifluoromethyl)sulfonyl)oxy)-4,6-di-O-benzoyl-β-D-galactopyranosyl)oxy)ethyl)carbamate [ No CAS ]
[ 10534-59-5 ]
benzyl (2-((2,3-di-O-acetyl-4,6-di-O-benzoyl-β-D-mannopyranosyl)oxy)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.5%	In N,N-dimethyl-formamide; toluene at 20℃;	60.C Step C: benzyl (2-((3,5-di-O-acetyl-4,6-di-O-benzoyl-β-D mannopyranosyl)oxy)ethyl)carbamate To a solution of benzyl (2-((((3,5-bis(trifluoromethyl)sulfonyl)oxy)-4,6-di-O- benzoyl-β-D galactopyranosyl)oxy)ethyl)carbamate (16.9 g, 20.37 mmol) in anhydrous toluene (100 mL), was added a solution of tetra butylammonium acetate (25 g, 82.9 mmol) in a mixture of toluene (150 mL) and DMF (4 mL) was added and the resulting mixture stirred at room temperature overnight. Diluted with of CH2Cl2 (30 mL) and washed with sat. NaCl (2 x 100mL), dried over MgSO4, filtered and evaporated. The residue was purified by silica gel column chromatography (Teledyne Isco : 330g) eluent: 0-50% EtOAc / Hexane (10cv) then 50% EtOAc / Hexane (5cv) to give the title compound (8 g, 60.5%).1H NMR (CDCl3) δ 8.10 (2H, m), 7.98 (2H, dd, J = 8.1 and 1.4 Hz), 7.61 (2H, m), 7.48 (2H, t, J = 7.8 Hz), 7.46 (2H, t, J = 7.7 Hz), 7.37 (4H, m), 7.33 (1H, m), 5.70 (1H, d, J = 3.3 Hz), 5.61 (1H, t, J = 10.0 Hz), 5.29 (1H, dd, J = 10.0 and 3.3 Hz), 5.26 (1H, m), 5.10 (2H, s), 4.79 (1H, s), 4.64 (1H, dd, J = 12.1 and 2.7 Hz), 4.47 (1H, dd, J = 12.1 and 5.8 Hz), 3.94 (2H, m), 3.74 (1H, m), 3.48 (1H, m), 3.37 (1H, m), 2.15 (3H, s), 2.00 (3H, s).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2016/164288, 2016, A1 Location in patent: Page/Page column 178; 179

56
[ 1452466-20-4 ]
[ 10534-59-5 ]
[ 1501977-14-5 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: {2-[([(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]oct-2-yl]carbonyl}amino)oxy]ethyl}carbamic acid tert-butyl ester With sulfur trioxide In N,N-dimethyl-formamide at 10 - 20℃; for 2.5h; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 2h;	2.3 Step 3: Preparation of (2S,5R)-N-(2-Boc-aminoethoxy)-6-(sulfooxy)-7-oxo-1 ,6-diaza-bicyclo [3.2.1 ]octane-2-carboxamide,tetrabutyl ammonium salt (VI): To a stirred solution of (2S,5R)-N-(2-Boc-aminoethoxy)-6-(hydroxy)-7 -oxo- 1 ,6-diaza- bicyclo[3.2.1]octane-2-carboxamide (V, 30.0 g, 0.0875 mol) in dimethylformamide (150 ml) was added sulphur trioxide dimethylformamide complex (16.06 g, 0.105 mol) in one portion, at 10°C. The reaction mass was stined at the same temperature for 30 minutes and then allowed to warm to room temperature. After 2 hours, a solution of tetrabutylammonium acetate (31.6 g, 0.105 mol) in water (95 ml) was slowly added to the reaction mixture and stined for another 2 hours. The solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The oily mass was co-evaporated with xylene (2 x 60 ml) to obtain thick mass. This mass was partitioned between 1: 1 mixture of dichloromethane (300 ml) and water (300 ml). The organic layer was separated and the aqueous layer re-extracted with dichloromethane (150 ml). The combined organic extracts were washed with water (3 x 150 ml) and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure and the resulting oily mass was triturated with ether (3 x 60 ml). Each time the ether layer was decanted and the residue was finally concentrated under reduced pressure to obtain the sticky mass. The so obtained material was purified by colunm chromatography over silica gel using mixture of methanol and dichloromethane as elution solvent. The solvent from the combined fractions was evaporated to obtain 47.5 g of (2S,5R)-N-(2-Boc-aminoethoxy)-6-(sulfooxy)- 7-oxo- 1 ,6-diaza-bicyclo [3.2.1 ]octane-2-carboxamide,tetrabutyl ammonium salt as white foam in 70% yield.Analysis:Mass: 423.4 (M-1) as free suiphonic acid; for Molecular Weight of 665.9 and Molecular Formula of C30H59N509 S;1H- NMR (400MHz, CDC13): (5 9.52(br s, 1H), 5.53(br s, 1H), 4.33(s, 1H), 3.95-3.92(m,3H),3.37-3.27(m, 11H), 2.87-2.84(d, 1H), 2.35-2.30(m, 1H), 2.17(m, 1H), 1.96-1.88(m, 2H), 1.74-1.60(m,8 H), 1.47-1.40(m, 17H), 1.02-0.98(m, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2016/120752, 2016, A1 Location in patent: Paragraph 15; 16

57
C₂₆H₄₃N₇O₉ [ No CAS ]
[ 10534-59-5 ]
(2S,5R)-N-[(2S)-3-[{tert-butoxycarbonyl}-amino]]-1-[{tertbutyl-(3R)-3-(hydrazinylcarbonyl)piperidine-1-carboxylate}-1-oxopropan-2-yl]-6-sulfooxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
610 mg	Stage #1: C₂₆H₄₃N₇O₉ With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In water; N,N-dimethyl-formamide for 2h;	1.8 Step 8: Synthesis of (2S,5R)-N-[(2S)-3-[{tert-butoxycarbonyl}-amino] -1- [{tertbutyl-(3R)-3- (hydrazinylcarbonyl) piperidine- 1-carboxylate)- 1-oxopropan-2-yl] -6-sulfooxy-7-oxo- 1,6- diazabicyclo [3.2. 1]octane-2-carboxamide tetrabutylammonium salt: Part 1:A solution of (2S,5R)-N-[(2S)-3- [ { tert-butoxycarbonyl} -aminoj -1- [ { tert-butyl-(3R)-3- (hydrazinylcarbonyl)piperidine- 1 -carboxylate)- 1 -oxopropan-2-ylj -6-benzyloxy-7-oxo- 1 ,6-diazabicyclo [3.2.ljoctane-2-carboxamide (600 mg, 0.873 mmol) in a 1:1 mixture of dichloromethane (3 ml) and N,N’dimethylformamide (3 ml) containing 10% palladium over carbon (180 mg, 50% wet) was hydrogenated at 55 psi for 2 hours at 25°C. The resulting mixture was filtered through a celite pad. The residue was washed with additional dichloromethane (90 ml). The solvent from the combined filtrate was evaporated under reduced pressure to obtain the debenzylated product as oil, which was used as such for the next reaction without further purification.Part 2:To a stirred solution of (2S,5R)-N- [(2S)-3-[ { tert-butoxycarbonyl} -aminoj -1- [ { tert-butyl-(3R)- 3 -(hydrazinylcarbonyl)piperidine- 1 -carboxylate)- 1 -oxopropan-2-ylj -6-hydroxy-7-oxo- 1,6-diazabicyclo[3.2.ljoctane-2-carboxamide (526 mg, 0.873 mmoles) in N,N’dimethylformamide (6 ml) was added sulphur trioxide dimethylformamide complex (160 mg, 1.04 mmol) in one portion, at 0°C under argon atmosphere. The reaction mass was stirred at the same temperature for 30 minutes and allowed to warm to room temperature. After 2 hours of stirring, to the resulting reaction mass was added a solution of tetrabutylammonium acetate (316 mg, 1.04 mmol) in water (1.2 ml). After 2 hours the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue.The oily mass was co-evaporated with xylene (2x10 ml) to obtain thick mass. This mass was partitioned between a 1:1 mixture of dichioromethane (50 ml) and water (50 ml). The organic layer was separated and the aqueous layer re-extracted with dichloromethane (50 ml). The combined organic extracts were washed with water (3x25 ml) and dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain crude product (- 1.05 g). This was purified by column chromatography over silica-gel (100-200 mesh) by eluting with 3% methanol in chloroform. The evaporation of the combined solvent fractions under reduced pressure gave 610 mg of the titled product as white foam in 74% yield.Analysis:Mass: 678.3 (M+1); for Molecular Formula of C27H45N708.C16H36N and Molecular Weight of677.

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/2089, 2017, A1 Location in patent: Page/Page column 28

58
[ 1436862-11-1 ]
[ 10534-59-5 ]
[ 135-02-4 ]
(2S,5R)-N'-[(2-methoxyphenyl)methylidene]-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
21.9%	Stage #1: trans-sulfuric acid mono-[2-hydrazinocarbonyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]ester; ortho-anisaldehyde With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 25℃; for 16h; Stage #2: tetrabutylammonium acetate In tetrahydrofuran at 25℃; for 22h;	1.1 Step-1: Synthesis of tetrabutylammonium salt of (25,5/?)-N'-[(2-methoxyphenyl)methylidene]- 7-oxo-6-(sulfooxy)-l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide: Step-1: Synthesis of tetrabutylammonium salt of (25,5/?)-N'-[(2-methoxyphenyl)methylidene]- 7-oxo-6-(sulfooxy)-l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide: To a clear solution of 2-methoxy benzaldehyde ( 0.971 g, 0.07 lmol) in tetrahydrofuran (20 ml), was added N, N-diisopropyl ethyl amine ( 2.47 ml, 0.0142 mol) followed by the addition of (25,5^)-7-oxo-6-(sulfooxy)- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide (2 g, 0.071 mol, was prepared according to the procedure described in Preparation 1) at 25°C under stirring. The reaction mixture was stirred for 16 hours and to the reaction mixture was added a solution of tetrabutyl ammonium acetate (2.14 g, 0.071 mol) in tetrahydrofuran (10 ml) and stirred further 25°C for 22 hours. The solvent was evaporated and the resulted residue was taken in dichloromethane (200 ml) and washed with 10% aqueous potassium hydrogen sulfate solution (100 ml x 2) and finally organic layer was washed with water (100 ml). The organic layer was collected and dried over anhydrous sodium sulfate and evaporated under reduced pressure to yield a semi solid mass. The material was purified by using column chromatography by eluting with 4% methanol in dichloromethane. The compound containing fractions were collected and on concentration yielded 1 g of tetrabutylammonium salt of {2S,5R)-N- [(2- methoxyphenyl)methylidene]-7-oxo-6-(sulfooxy)- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide as a white solid in 21.9% yield. Analysis: 397.2 (M-l) as free acid; for Molecular Weight of 639.86 and Molecular Formula of 1H NMR (CDCI3): δ 9.66 (s, 1H), 8.47(s, 1H), 8.08 (d, 1H, / = 7.6 Hz ), 7.37 (t, 1H, J = 7.2 Hz), 6.98 (t, 1H, J = 7.2 Hz ), 6.90 (d, 1H, / = 8.4 Hz), 4.38 (s, 1H), 4.06-4.02 (m, 1H), 3.90 (s, 3H), 3.44-3.28 (m, 9H), 2.90-2.86 (m, 1H), 2.54-2.48 (m, 1H), 2.24-2.16 (m, 1H) 2.00- 1.86 (m, 1H), 1.80-1.40 (m, 17H), 1.08 (t, 12H, = 7.2 Hz ).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/2083, 2017, A1 Location in patent: Page/Page column 23

59
[ 1436862-11-1 ]
lithium [4-(tertiary-butyldimethylsilanyloxymethyl)-2H-1,2,3-triazol-2-yl]acetic acid [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-N’-{ [4-((tertiary-butyldimethylsilanyloxy)methyl)-2H-1,2,3-triazol-2-yl]acetyl}-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In water; N,N-dimethyl-formamide at 25 - 30℃; for 1h;	43.1 Step 1; Synthesis tetrabutylammonium salt of (2S,5R)-N'-[4-(tertiary-butyl-dimethyl- silanyloxymethyl)-2H-l,2,3-triazol-2-yl]acetyl}-7-oxo-6-(sulfooxy)-l,6-diazabicyclo[3.2.1] octane-2-carbohydrazide To a solution of (2S,5 ?)-7-oxo-6-(sulfooxy)- l,6- diazabicyclo[3.2.1]octane-2-carbohydrazide (3.6 g, 12.8 mmol, prepared as per the reference WO2013030733) in dimethylformamide (18 ml) was added N,N-diisopropylethylamine (6.7 ml) under stirring at 25-30°C. The lithium salt of [4-(tertiary-butyl-dimethyl-silanyloxy methyl)-2H- l,2,3-triazol-2-yl]acetic acid (3.5 g, 12.8 mmol , product from preparation 37) was added as solid under stirring followed by EDC.HCl (3.7 g, 19.3 mmol) and HOBT (1.95 g, 12.7 mmol) at 25-30 °C. The progress of reaction was monitored by TLC (chloroform: methanol, 9: 1). After complete consumption of starting material a solution of tetrabutyl ammonium acetate (5.8 g, 19.2 mmol) in water (20 ml) was added and stirred for 1 hour. Dimethylformamide was distilled out completely and co-evaporated with xylene (2x25 ml). The concentrated mass thus obtained was poured on to water (36 ml) containing N-methyl morpholine (1 ml) under stirring and extracted with DCM (2x40 ml). The organic extracts were combined and washed with water (1x25 ml), dried over anhydrous sodium sulfate. The volatiles were removed under reduced pressure to get 4.5 g of crude compound which was further purified by column chromatography (100-200 mesh size silica gel) using dichloromethane: methanol as an eluent. Pure fractions were collected and concentrated to yield 1.8 g of tetrabutylammonium salt of (2S,5R)-N'-{ [4-(tertiary-butyl-dimethyl- silanyloxymethyl)-2H- l,2,3-triazol-2-yl]acetyl}-7-oxo-6-(sulfooxy)- l,6-diazabicyclo[3.2.1]octane- 2-carbohydrazide in 14% yield. Analysis: Mass: 534.4 (M- l) as free acid; for Molecular weight: 774 and Molecular formula: C34H66N808SSi.

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 69

60
(2S,5R)-6-hydroxy-N'-(1H-imidazol-1-ylacetyl)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-N’-(1H-imidazol-1-ylacetyl)-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54.15%	With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 10 - 15℃;	2.5 Step 5: Synthesis of tetrabutyl ammonium salt of (25,5/f)-N'-(lH-imidazol-l-ylacetyl)-7-oxo- 6-(sulfooxy)-l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide: To a stirred solution of (25,5 ?)-6- hydroxy-A^-(lH-imidazol- l-ylacetyl)-7-oxo- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide (10.3 g, 33.4 mmol, product obtained in step 4) in dimethylformamide (70 ml) was added dimethylformamide sulfur trioxide complex (6.45 g, 42.1 mmol). The reaction mixture was stirred at 10- 15°C. The progress of reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (8:2) as solvent. After completion of the reaction, solution of tetrabutyl ammonium acetate (12.69 g, 42 mmol) in water (43 ml) was added to the reaction mixture under stirring. After complete conversion to tetrabutylammoinum salt, the volatiles were removed under vacuum at 40-45 °C. The obtained residue was partitioned in mixture of dichloro methane and water (140 ml + 140 ml). The organic layer was dried over anhydrous sodium sulfate and distilled to get 23 g of crude product. The crude product was purified by column chromatography using 100-200 mesh silica gel using mixture of chloroform and methanol as an eluent. The pure fractions were collected and were concentrated to obtain 12 g of tetrabutyl ammonium salt of (2S,5R)-iV-(lH- imidazol- l-ylacetyl)-7-oxo-6-(sulfooxy)- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide in 54.15% yield

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 52

61
(2S,5R)-6-(hydroxy)-7-oxo-N’-(1H-tetrazol-1-ylacetyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-6-(sulfooxy)-7-oxo-N'-( 1H-tetrazol-1-ylacetyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	Stage #1: (2S,5R)-6-(hydroxy)-7-oxo-N’-(1H-tetrazol-1-ylacetyl)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In water at 25 - 30℃;	3.7 Step 7: Synthesis of tetrabutyl ammonium salt of (25,5/f)-6-(sulfooxy)-7-oxo-N'-(lH-tetrazol- l-ylacetyl)-l,6-diazabicyclo [3.2.1]octane-2-carbohydrazide To a stirred solution of (25,5 ?)-Λ^- [(5-ieri-butoxycarbonylamino-lH-tetrazol-l-yl)acetyl]-7-oxo-6-oxy-l,6-diazabicyclo[3.2.1] octane-2-carbohydrazide (4.65 g, 1.5 mmol, product from Step 6) in dimethylformamide (30 ml) was added dimethylformamide sulfur trioxide complex (2.76 g, 1.8 mmol) in one portion at 0°C under argon atmosphere. The reaction mass was stirred at the same temperature for 30 minutes and allowed to attain ambient temperature. The reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (9: 1) as solvent. After complete consumption of starting material tetrabutyl ammonium acetate (5.42 g, 1.8 mmol) dissolved in 20 ml of water was added to it at 25-30 °C under stirring. The reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (9: 1) as solvent. After complete consumption of starting material the volatiles were removed under reduced pressure. The residue was partitioned between dichloromethane (200 ml) and water (100 ml). The water layer was separated and organic layer washed with water (100 ml). The organic extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide 7.8 g of tetrabutyl ammonium salt of (2S,5R)-6- (sulfooxy)-7-oxo-N'-(lH-tetrazol- l-ylacetyl)- l,6-diaza bicycle [3.2.1]octane-2-carbohydrazide in 82% yield. Analysis: 9.3 (M- l) for free acid; for Molecular weight: 631 and Molecular formula: CioHi3N807S. (400MHz, DMSO-d6): S 7.93 (s, 1H), 5.33 (s, 2H), 3.97 (bs, 1H), 3.83(m, 1H), 3.14-3.10 (m, 9H), 2.87(m, 1H), 2.11- 1.5 (m, 4H), 1.54 (m, 8H), 1.33- 1.24 (m, 8H), 0.93-0.89 (m, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 54; 55

62
(2S,5R)-N’-[(5-tert-butoxycarbonylamino-1H-tetrazol-1-yl)acetyl]-7-oxo-6-hydroxy-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]
[ 10534-59-5 ]
tetra-butylammonium (2S,5R)-N’-[(5-tert-butoxycarbonylamino-1H-tetrazol-1-yl)acetyl]-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	Stage #1: (2S,5R)-N’-[(5-tert-butoxycarbonylamino-1H-tetrazol-1-yl)acetyl]-7-oxo-6-hydroxy-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In water at 25 - 30℃;	24.5 Step 5: Synthesis of tetrabutyl ammonium salt of (25,5/?)-N'-[(5-tgrt-butoxycarbonylamino- lH-tetrazol-l-yl)acetyl1-7-oxo-6-(sulfooxy)-l,6-diazabicyclo[3.2.11 octane-2-carbohydrazide To a stirred solution of (25,5 ?)-N'-[(5-ieri-butoxycarbonylamino- lH-tetrazol- l-yl)acetyl]-7-oxo-6- hydroxy- l,6-diazabicyclo[3.2.1] octane-2-carbohydrazide (1.15 g, , 2.7 moles, product from Step 4) in dimethylformamide (14 ml) was added dimethyl sulfur trioxide complex (500 mg, 3.2 mmol) in one portion under stirring in presence of argon atmosphere at 0°C. The reaction mass was stirred at the same temperature for 30 minutes and allowed to attain ambient temperature. The progress of reaction was monitored by performing thin layer chromatography using mixture of chloroform and methanol (9: 1) as solvent. After complete consumption of the starting material tetrabutyl ammonium acetate (1 g, 3.2 mmol) dissolved in water (3 ml) was added to the reaction mixture under stirring at 25-30 °C. The reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (9: 1). After complete consumption of starting material the volatiles were removed under reduced pressure. The residue obtained was partitioned between dichloromethane (140 ml) and water (140 ml). The water layer was separated and organic layer washed with water (70 ml). The collective organic extract was dried and concentrated under reduced pressure to provide 1.45 g of the titled product as off-white foam in 72% yield. Analysis: Mass spectrum: 504.3 (M- l), 506.2 (M+l) for free acid, for Molecular weight: 746 and for Molecular formula: C15H22N9O9S. Ci6H36N; 1HNMR(400MHz, DMSO-d6): £ 5.16 (s, 2H), 3.98 (bs, 1H), 3.83 (m, 1H), 3.18-3.10 (m, 9H), 2.99 (m, 1H), 2.02- 1.65 (m, 4H), 1.58 (m, 8H), 1.46 (s, 9H), 1.35- 1.26 (m, 8H), 0.95-0.91 (m, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 62

63
(2S,5R)-6-hydroxy-N'-[5-(2-tert-butyldimethylsilanyloxyethyl)-1H-tetrazol-1-yl]acetyl}-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carbohydrazide [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-N’-[5-(2-tert-butyldimethylsilanyloxyethyl)-1H-tetrazol-1-yl]acetyl}-7-oxo-6-sulfooxy-1,6-diazabicyclo [3.2.1]octane-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 30℃; for 3h; Inert atmosphere;	38.2 Step 2: Synthesis of Tetrabutylammonium salt of (25,5/f)-N'-[5-(2-tert- butyldimethysilanyloxyethyl)-lH-tetrazol-l-yl]acetyl}-7-oxo-6-sulfooxy-l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide: To a solution of (25,5 ?)-6-benzyloxy-N'-{ [5-(2-tert- butyldimethysilanyloxyethyl)- lH-tetrazol- l-yl]acetyl}-7-oxo- l,6-diazabicyclo[3.2.1]octane-2- carbohydrazide (8 g, 14.3 mmol) in dimethylformamide (40 ml) and dichloromethane (40 ml) was added 10% Pd/C(50% wet basis) 2.4 g at 25- 30 °C. The H2 gas was bubbled through the reaction mixture under stirring. The progress of reaction was monitored by TLC (chloroform: methanol, 9: 1). The catalyst was removed by filtration on celite bed and washed with mixture of dichloromethane and dimethylformamide (1 : 1, 2x20 ml). The filtrate was concentrated under reduced pressure yielded (25,5 ?)-6-hydoxy-N'-{ [5-(2-tert-butyldimethysilanyloxyethyl)- lH- tetrazol- l-yl]acetyl}-7-oxo- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide (6.6 g, c.a 100% yield used for next reaction as such). The product (25,5 ?)-6-hydoxy-N'-{ [5-(2-tert- butyldimethysilanyloxyethyl)- lH-tetrazol- l-yl]acetyl}-7-oxo- l,6-diazabicyclo[3.2.1]octane-2- carbohydrazide (6.6 g, 14.3 mmol) thus obtained was dissolved in dimethylformamide (40 ml) was added dimethylformamide sulfur trioxide complex (2.63 g, 17.20 mmol) in argon atmosphere at 0°C under stirring. The progress of reaction was monitored by TLC (chloroform: methanol, 9: 1). After completion of the reaction added a solution of tetra-butyl ammonium acetate (5.18 g, 17.20 mmol) dissolved in water (18 ml) at 25-30°C. The reaction mixture was stirred for 3 hours and concentrated under reduced pressure. The residue obtained was taken in dichloromethane (80 ml) and washed with water (2x40 ml). The organic extract was dried on anhydrous sodium sulfate and concentrated to yield crude tetrabutylammonium salt of (2S,5 ?)- V-{ [5-(2-tert- butyldimethysilanyloxyethyl)- lH-tetrazol- l-yl]acetyl}-7-oxo-6-sulfooxy- l,6-diazabicyclo[3.2.1] octane-2-carbohydrazide. This material was purified by column chromatography (silica gel 100-200 mesh size) using chloroform: methanol as an eluent. The fractions containing the product obtained at 5% methanol in chloroform. The pure fractions were combined and concentrated to get 7.5 g of tetrabutylammonium salt of (25,5 ?)-N'-{ [5-(2-tert-butyldimethysilanyloxyethyl)- lH-tetrazol- l- yl]acetyl}-7-oxo-6-sulfooxy- l,6-diazabicyclo[3.2.1]octane-2-carbohydrazide as off-white foam solid in 66% yield.

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 66; 67

64
(2S,5R)-6-(benzyloxy)-7-oxo-N-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-7-oxo-6-(sulfooxy)-N-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: (2S,5R)-6-(benzyloxy)-7-oxo-N-[2-(2H-1,2,3-triazol-2-yl)ethoxy]-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen In dichloromethane; N,N-dimethyl-formamide for 3h; Stage #2: With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 20℃; for 1h; Stage #3: tetrabutylammonium acetate In water at 0℃; for 1h;	45.4 Step 4: Synthesis Tetrabutyl ammonium salt of (25,5/f)-7-oxo-6-(sulfooxy)-N-[2-(2H-l,2,3- triazol-2-yl)ethoxy]-l,6-diazabicyclo[3.2.1]octane-2-carboxamide: To a solution of (25,5 ?)-6- (benzyloxy)-7-oxo-N-[2-(2H-l,2,3-triazol-2-yl)ethoxy]-l,6-diazabicyclo[3.2.1]octane-2- carboxamide (4 g, 10.3 mmol, upper spot as per thin layer chromatography in Step 3) in dimethylformamide (20 ml) and dichloromethane (20 ml) was added palladium over carbon (10%, 1.0 g) under nitrogen atmosphere. The reaction mixture was flushed with hydrogen gas and stirred for 3 hour under hydrogen pressure (55 psi). The progress of reaction was monitored by thin layer chromatography using mixture of chloroform and methanol (9: 1) as solvent system. After complete conversion, the reaction mixture was filtered through celite bed and washed with a mixture of dichloromethane and dimethylformamide (20 ml, 1: 1). The collected filtrate was evaporated under reduced pressure to dryness. The intermediate thus obtained was dissolved into dimethylformamide (20 ml) and dimethylformamide sulfur trioxide complex (2.4 g, 15.6 mmol) was added under stirring at 0 °C. The reaction mixture was allowed to attain ambient temperature and stirred further for 1 hour. The completion of reaction was monitored by performing thin layer chromatography using mixture of chloroform and methanol as solvent system. After complete conversion, the reaction mixture was cooled to 0°C and then a solution of tetra butyl ammonium acetate (5 g, 16.5 mmol) in water (17 ml) was slowly added under stirring. After 1 hour, the reaction mixture was concentrated to dryness in vacuum and co-evaporated with xylene (2x30 ml) to dimethylformamide free mass. To this concentrated mass, water (40 ml) was added and then extraction with dichloromethane was carried (2x40 ml). The collective organic layer was dried on anhydrous sodium sulfate and concentrated to dryness to provide 8.5 g of crude compound. It was purified using column chromatography (silcagel 60- 120) by using mixture of dichloromethane and methanol as an eluent. The pure compound was isolated at 5% concentration of methanol in dichloromethane; the collective fractions were collected and evaporated to obtain 3.5 g of tetrabutyl ammonium salt of (25,5 ?)-7-oxo-6-(sulfooxy)-N-[2-(2H- l,2,3-triazol-2-yl)ethoxy]- l,6-diazabicyclo[3.2.1]octane- 2-carboxamide in 55% yield. Analysis: Mass: 375.2 (M- l, for free acid) for Molecular weight: 617 and Molecular formula: C27H5iN707S.

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/81615, 2017, A1 Location in patent: Page/Page column 73; 74

65
(2S,5R)-N-{ [1-tert-butoxycarbonyl (2R,4S)-4-(morpholin-4-yl)pyrrolidin-2-yl]methoxy}-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide tetrabutylammonium salt [ No CAS ]
[ 10534-59-5 ]
(2S,5R)-N-{ [1-tert-butoxycarbonyl (2R,4S)-4-(morpholin-4-yl)pyrrolidin-2-yl]methoxy}-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide tetrabutylammonium salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	Stage #1: (2S,5R)-N-{ [1-tert-butoxycarbonyl (2R,4S)-4-(morpholin-4-yl)pyrrolidin-2-yl]methoxy}-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide tetrabutylammonium salt With sulfur trioxide-N,N-dimethylformamide complex In N,N-dimethyl-formamide at 0 - 25℃; for 1.16667h; Stage #2: tetrabutylammonium acetate In water for 1h;	2.8 Step 8: Synthesis of tetrabutylammonium salt of (2S,5R)-N-{ [1-tert-butoxycarbonyl (2R,4S)-4- (morpholin-4-yl)pyrrolidin-2-yl]methoxy}-7-oxo-6-(sulfooxy)- 1,6-diazabicyclo[3.2. 1]octane-2-carboxamide To a stirred solution of a tetrabutylammonium salt of (2S,5R)-N-[1-tert-butoxycarbonyl (2R, 4S)-4-(morpholin-4-yl)pyrrolidin-2-ylj methoxy } -6-hydroxy-7-oxo- 1,6- diazabicyclo[3.2.ljoctane-2-carboxamide (1.5 g, 0.0032 mol) in dimethylformamide (15 ml) was added sulfur trioxide: dimethylformamide complex (1.0 g, 0.0064 mol) under stirring at temperature of about 0 °C. The reaction mixture was stirred at 0 °C for 10 minutes and then allowed to warm to 25°C. After 1 hr of stirring a solution of tetra butyl ammonium acetate (2.89 g, 0.0096 mol) in water (8 ml) was added to the reaction mixture under continuous stirring. After completion of 1 hr stirring the solvent from the reaction mixture was evaporated under reduced pressure to obtain an oily residue. The residue obtained was then purified by silica gel(60-120 mesh size) column chromatography using 6% Methanol: DCM mixture as an eluant to get required compound. The solvent of the combined fractions were evaporated to provide 1.2 g of the titled compound as white solid, 47% yield. Analysis:Mass: 548.4 (M-1) as free acid; for Molecular weight: 791.07 and Molecular formula:C37H70N60 ftS‘H NMR (CDC13, 400 MHz): 5 10.42 (brs, 1H), 4.38-4.28 (m, 1H), 3.98-3.92 (m, 1H), 3.86- 3.68 (m, 5H), 3.62-3.52 (m, 1H), 3.42-3.20 (m, 1OH), 2.98-2.84 (m, 2H), 2.58-2.32 (m, 5H), 2.24-2.14 (m, 1H), 1.96-1.84 (m, 2H), 1.84-1.62 (m, 12H), 1.56-1.42 (m, 17H), 1.06-0.97 (m, 12H).

Reference： [1]Current Patent Assignee: WOCKHARDT LIMITED - WO2017/98425, 2017, A1 Location in patent: Page/Page column 33

66
[ 2743-00-2 ]
[ 10534-59-5 ]
[ 114897-91-5 ]
2-(2′-acetyl-3-fluoro[1,1′-biphenyl]-4-yl)acetonitrile [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2017,vol. 2017,p. 6274 - 6282

67
{nBu₄N}₄[V₁₂O₃₂(CH₃NO₂)] [ No CAS ]
[ 10534-59-5 ]
[ 661-36-9 ]
C₂H₃O₂^(1-)*O₃₂V₁₂^(4-)*5C₈H₂₀N⁽¹⁺⁾ [ No CAS ]

Reference： [1]Chemistry - An Asian Journal,2017,vol. 12,p. 1909 - 1914

68
C₁₄H₁₉S⁽¹⁺⁾ [ No CAS ]
[ 10534-59-5 ]
[ 123630-52-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	In dichloromethane at -78 - 20℃; for 1h; Inert atmosphere; Electrochemical reaction;	Reactions of thiirenium ion with nucleophiles General procedure: The electrolysis of PhSSPh (27.3 mg, 0.125 mmol) in thepresence of 4-octyne (28.6 mg, 0.250 mmol) was carried out as described above. To a solution of thethiirenium ion thus generated in the anodic chamber was added a solution of nucleophile (2.50 mmol) inCH2Cl2 at -78 °C and the reacFon mixture was sFrred at -78 °C for 30 min, and then at 20 °C for 30 min. Thesolution in the anodic chamber was collected and the solvent was removed under reduced pressure and theresidue was quickly filtered through a short column (2 x 3 cm) of silica gel to remove Bu4NBF4. After removal ofthe solvent under reduced pressure, the crude product was purified by flash chromatography and GPC toobtain the products.

Reference： [1]Shimizu, Akihiro; Horiuchi, Shun; Hayashi, Ryutaro; Matsumoto, Kouichi; Miyamoto, Yu; Morisawa, Yusuke; Wakabayashi, Tomonari; Yoshida, Jun-Ichi [Arkivoc, 2017, vol. 2018, # 2, p. 97 - 113]

69
(R)-3-[(S)-N-(Benzyl)pyrrolidin-2-yl]-1,1,1-trifluoropropan-2-ol [ No CAS ]
[ 10534-59-5 ]
(2S,4R)-1-benzyl-2-(trifluoromethyl)azepan-4-yl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: (R)-3-[(S)-N-(Benzyl)pyrrolidin-2-yl]-1,1,1-trifluoropropan-2-ol With trifluoromethylsulfonic anhydride; N,N,N',N'-tetramethyl-1,8-diaminonaphthalene In dichloromethane at 40℃; for 5h; Inert atmosphere; Sealed tube; Stage #2: tetrabutylammonium acetate In dichloromethane at 20℃; for 0.0833333h; Inert atmosphere; Sealed tube;

Reference： [1]Masson, Guillaume; Rioton, Sarah; Gomez Pardo, Domingo; Cossy, Janine [Organic Letters, 2018, vol. 20, # 16, p. 5019 - 5022]

70
benzyl-2-O-acetyl-3-trifluoromethanesulfonyl-4,6-O-benzylidene-β-D-galactopyranoside [ No CAS ]
[ 10534-59-5 ]
benzyl-2,3-O-acetyl-4,6-O-benzylidenegulopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	In N,N-dimethyl-formamide at 50℃; for 6h; Inert atmosphere;	1.3; 2.3; 3.3 (3) preparation of Benzyl- 2- ,3- O- acetyl- 4,6- O- benzylidene- β - L- Gulopyranoside (G- 5) Under nitrogen protection, 8.8 g of G- 4 (16.5 mmoL) and 10 g of tetrabutylammonium oxide acetyl were dissolved in 200 mL of dry DMF and warmed to 50 °C, and after 6 hours of reaction, TLC monitored the G- 4 consumption progress. After completion, it was poured into 300 mL of ethyl acetate and 200 mL of water, and the mixture was thoroughly stirred to separate the layers. The organic layer was washed twice with 300 mL of water and once with 100 mL of Saturated brine, dried over anhydrous sodium sulfate for 5 hours, filtrated, and concentrated under reduced pressure to give a red oil, and 6.3 g of a white solid by column chromatography (petroleum ether / ethyl acetate = 3 / 1, V / V), i.e. Benzyl- 2- ,3- O- acetyl- 4,6- O- benzylidene- β - L- Gulopyranoside (G- 5) , yield 86%.

Reference： [1]Current Patent Assignee: GUANGZHOU UNIVERSITY OF CHINESE MEDICINE - CN108948106, 2018, A Location in patent: Page/Page column 10-14

71
[ 20469-65-2 ]
[ 1270874-89-9 ]
[ 10534-59-5 ]
2‑[1‑(4‑methoxybenzyl)‑5‑(3,5‑dimethoxyphenyl)‑1H‑1,2,3‑triazol‑4‑yl]ethyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With palladium diacetate In 1-methyl-pyrrolidin-2-one at 110℃; for 24h; Inert atmosphere;	2-[1-(4-Methoxybenzyl)-5-(3,5-dimethoxyphenyl)-1H-1,2,3-triazol-4-yl]ethyl acetate (6, C22H25N3O5) To a solutionof 5 (1 mmol, 1 eq.), 1-bromo-3,5-dimethoxybenzene(1.5 eq.), TBAA (6.0 eq.), Pd(OAc)2 (0.1 eq.) were dissolvedin 2 cm3 of NMP under an argon atmosphere. The wholewas heated at 110 °C for 24 h. After cooling, a saturatedsolution of Na2CO3 was added and the resulting solutionwas extracted thrice with ethyl acetate. The organic layerswere then dried over Na2SO4 and evaporated to give anoil, from which residual NMP was evacuated using a lyophilizer.Chromatography of the resulting oil on silica geleluted with hexane/ethyl acetate (v/v: 60/40) gave 7 (tracesin these conditions). Further elution gave 6 in 75% yield asan orange oil. MS (ESI): m/z = 412.10 ([M+H]+); 1H NMR(400 MHz CDCl3):= 1.77 (s, 3H), 2.80 (t, 2H, J = 6.9 Hz),3.55 (s, 6H), 3.58 (s, 3H), 4.14 (t, 2H, J = 6.9 Hz), 5.29(s, 2H), 6.21 (d, 2H, J = 2.3 Hz), 6.46 (t, 1H, J = 2.3 Hz),6.72 (d, 2H, J = 8.7 Hz), 6.93 (d, 2H, J = 8.7 Hz) ppm; 13CNMR (100 MHz, CDCl3):= 20.7, 24.8, 51.5; 55.1, 55.3,63.3, 101.3, 107.6, 113.9,127.6,128.6, 128.8, 135.1, 141.6,159.3, 160.9, 170.6 ppm.

Reference： [1]Praud-Tabariès, Annie; Bottzeck, Olivier; Blache, Yves [Monatshefte fur Chemie, 2019, vol. 150, # 4, p. 649 - 654]

72
[ 1270874-89-9 ]
[ 10534-59-5 ]
2‑[1‑(4‑methoxybenzyl)‑1H‑1,2,3‑triazol‑4‑yl]ethyl acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With palladium diacetate In 1-methyl-pyrrolidin-2-one at 110℃; for 24h; Inert atmosphere;	2-[1-(4-Methoxybenzyl)-1H-1,2,3-triazol-4-yl]ethyl acetate(7, C14H17N3O3) To a solution of 5 (1 mmol, 1 eq.), TBAA(2.0 eq.), Pd(OAc)2 (0.1 eq.) were dissolved in 2 cm3 ofNMP under an argon atmosphere. The whole was heatedat 110 °C for 24 h. After cooling, a saturated solution ofNa2CO3was added and the resulting solution was extractedthrice with ethyl acetate. The organic layers were thendried over Na2SO4and evaporated to give an oil, fromwhich the residual NMP was evacuated using a lyophilizer.A flash chromatography on silica gel eluted with hexane/ethyl acetate (v/v: 60/40) gave 7 (81%) as an orange oil.MS (ESI): m/z = 298.04 ([M + Na]+); 1H NMR (400 MHz CDCl3):= 1.96 (s, 3H), 2.99 (t, 2H, J = 6.8 Hz), 3.76 (s,3H), 4.26 (t, 2H, J = 6.8 Hz), 5.39 (s, 2H), 6.85 (d, 2H,J = 8.6 Hz), 7.18 (d, 2H, J = 8.6 Hz), 7.23 (s, 1H) ppm; 13CNMR (100 MHz CDCl3):= 20.9, 25.5, 53.6, 55.3, 63.2,114.4, 121.2, 126.7, 129.6, 144.3, 159.9, 170.9 ppm.

Reference： [1]Praud-Tabariès, Annie; Bottzeck, Olivier; Blache, Yves [Monatshefte fur Chemie, 2019, vol. 150, # 4, p. 649 - 654]

73
N,N-dibenzyl-(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
88.7%	Stage #1: N,N-dibenzyl-(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen; sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol at 20℃; for 1h; Autoclave; Stage #2: tetrabutylammonium acetate With acetic acid In water at 20℃;	9 Example 9: ([(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octane-6-yl]oxy) Preparation of sulfonyl) tetrabutylammonium salt (II) To a stainless steel reaction vessel, 14 g of isopropanol, 17 g of water, and 4.9 g (0.01 mol) were prepared according to the method of Example 5.N,N-dibenzyl-(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (VI1), 1.56 g (0.0112 mol) of trimethylamine trioxide, 0.2 g (0.002 mol) of triethylamine, 0.11 g of palladium Mass content is10% palladium on carbon (water content is 55 wt%). After the kettle is filled, nitrogen is protected. Intermittent hydrogenation is carried out to maintain the hydrogen pressure at 0.07-0.13 MPa, and the temperature is maintained at room temperature for 1 hour until the reaction of the raw material VI1 is complete (the pressure will increase). After replacing with nitrogen,The temperature was kept at room temperature for 1.5 hours. After neutralizing by adding 0.16 g (0.0026 mol) of acetic acid, palladium carbon was filtered off, and the cake was washed with 8.6 g of water. The filtrate was washed with 26 ml of n-butyl acetate and the aqueous phase was separated.

Reference： [1]Current Patent Assignee: XINFA PHARMACEUTICAL CO LTD - CN109678855, 2019, A Location in patent: Paragraph 0102-0105

74
N,N-bis(p-methoxy)benzyl (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
92.7%	Stage #1: N,N-bis(p-methoxy)benzyl (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen; sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol at 20℃; for 1h; Stage #2: tetrabutylammonium acetate With acetic acid In water at 20℃;	10 Example 10: ([(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octane-6-yl]oxy}sulfonyl) Preparation of tetrabutylammonium salt (II) n the hydrogenation reactor, 16 g of isopropanol, 20 g of water, and 4.9 g (0.01 mol) of N,N-di(p-methoxy)benzyl-(2S,5R)-6-benzyloxyprepared in Example 7 were added.-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (VI2),1.56 g (0.0112 mol) of trimethylamine sulfur trioxide, 0.2 g (0.002 mol) Triethylamine, 0.12 g ofpalladium on carbon having amass content of 10%(water content: 55 wt%).After the kettle is filled, nitrogen is protected.Intermittent hydrogenation was carried out to maintain the hydrogen pressure at 0.07-0.13MPa, and the temperature was kept at room temperature for 1 hour until thereaction of theraw material VI2 wascomplete (the pressure would increase).After replacement with nitrogen, the temperature waskeptat room temperature for1.5 hours.After neutralizing by adding 0.16 g (0.0026 mol) of acetic acid, palladium carbon was filtered off, and the cake was washed with 10 g of water.The filtrate was washed with 30 ml of n-butyl acetate and the aqueous phase was separated.

Reference： [1]Current Patent Assignee: XINFA PHARMACEUTICAL CO LTD - CN109678855, 2019, A Location in patent: Paragraph 0106-0108

75
Ν,Ν-bis(p-methyl)benzyl (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
86.8%	Stage #1: Ν,Ν-bis(p-methyl)benzyl (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With palladium 10% on activated carbon; hydrogen; sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol at 20℃; for 1h; Stage #2: tetrabutylammonium acetate With acetic acid In water at 20℃;	11 Example 11: ([(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octane-6-yl]oxy}sulfonyl) Preparation of tetrabutylammonium salt (II) In the hydrogenation reactor, 15 g of isopropanol, 18 g of water, and 4.6 g (0.01 mol) of N,N-bis(p-methyl)benzyl-(2S,5R)-6-benzyl prepared in Example 8 were added. Oxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide (VI3),1.56 g (0.0112 mol) of trimethylamine sulfur trioxide, 0.2 g (0.002 mol) of triethylamine, 0.11 g of palladium carbon having a mass content of 10% palladium (water content: 55 wt%). After the kettle is filled, nitrogen is protected. Intermittent hydrogenation is carried out to maintain the hydrogen pressure at 0.07-0.13 MPa, and the temperature is maintained at room temperature for 1 hour until the reaction of the raw material VI3 is complete (the pressure will increase). After replacement with nitrogen, the temperature was kept at room temperature for 1.5 hours. After neutralizing by adding 0.16 g (0.0026 mol) of acetic acid, palladium carbon was filtered off, and the cake was washed with 8.6 g of water. The filtrate was washed with 26 ml of n-butyl acetate and the aqueous phase was separated.

Reference： [1]Current Patent Assignee: XINFA PHARMACEUTICAL CO LTD - CN109678855, 2019, A Location in patent: Paragraph 0109-0111

76
(2S,5R)-6-(methoxymethyloxy)-7-oxo-1,6-diazacyclo[3.2.1]octane-2-carboxamide [ No CAS ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
91.5%	With sulfur trioxide trimethylamine complex; triethylamine In water; isopropyl alcohol at 10 - 20℃; for 4h;	1.5; 1.5 Step (5):[(2S,5R)-2-carbamoyl-7-oxo-1,6-diazacyclo[3.2.1]octane-6-yl]oxy}sulfonyltetra-n-butylammonium salt Preparation of (VII) Add 100 g of isopropyl alcohol to a 500 ml four-necked flask equipped with a stirring and thermometer.2.0 g of water, 23.0 g (0.1 mol) of (2S,5R)-6-methoxymethyloxy-7-oxo-1,6-diaza heterocycle prepared by the method of step (4) [3.2.1 Octane-2-carboxamide, 5.0 g of triethylamine,36.0 g (0.12 mol) of tetrabutylammonium acetate at 10-15 ° C,Add 46.5 g (0.25 mol) of sulfur trioxide trimethylamine complex,The reaction was stirred for 4 hours between 15 and 20 ° C, and the reaction liquid was poured into 150 g of dichloromethane and 150 g of ice water mixture.Add acetic acid to adjust the pH of the system to 3.5-2.5, layer, and extract the water layer twice with dichloromethane.50 grams each time.Combine the organic phase,The saturated sodium chloride solution was washed twice with 20 g each time, and after the obtained organic phase was recovered, the residue was recrystallized from 50 g of dichloromethane-methyl isobutyl ketone (1:3 by volume).46.3 g of [(2S,5R)-2-carbamoyl-7-oxo-1,6-diazacyclo[3.2.1]oct-6-yl]oxy}sulfonyltetra-n-butyl The ammonium salt had a liquid phase purity of 99.9% and a yield of 91.5%.

Reference： [1]Current Patent Assignee: XINFA PHARMACEUTICAL CO LTD - CN109956941, 2019, A Location in patent: Paragraph 0089; 0105-0107; 0129; 0154-0159

77
(2S,5R)-2-(difluoromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-2-(difluoromethyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.45 g	Stage #1: (2S,5R)-2-(difluoromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one With sulfur trioxide trimethylamine complex; triethylamine In dichloromethane at 0℃; for 4h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In dichloromethane; water at 20℃; for 2h; Inert atmosphere;	2.f f. Tetrabutylammonium (2S,5R)-2-(difluoromethyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate A solution of (2S,5R)-2-(difluoromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one (0.40g, 2.1 mmol) in DCM (30 mL) at 0°C was treated with TEA (1.1 mL, 8.3 mmol) then sulfur trioxide pyridine complex (0.67g, 4.2 mmol) was added. After 4h at room temperature a solution of n-tetrabutylammonium acetate (0.94g, 3.1 mmol) in water (20 mL) was added. After 2h further DCM was added and the phases were separated. The DCM phase was washed with water, dried (Na2SO4) and evaporated. The residue was chromatographed on silica eluting with 0-100% ethyl acetate in hexane followed by 4% methanol in DCM, affording a colourless oil (0.45g, 42% over 2 steps). M/z 271.4 (M-)
0.45 g	Stage #1: (2S,5R)-2-(difluoromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one With sulfur trioxide pyridine complex; triethylamine In dichloromethane at 0℃; for 4h; Stage #2: tetrabutylammonium acetate In dichloromethane; water at 20℃; for 2h;

Reference： [1]Current Patent Assignee: ANTABIO SAS - EP3608318, 2020, A1 Location in patent: Paragraph 0080; 0095; 0107-0108
[2]Davies, David T.; Leiris, Simon; Zalacain, Magdalena; Sprynski, Nicolas; Castandet, Jérôme; Bousquet, Justine; Lozano, Clarisse; Llanos, Agustina; Alibaud, Laethitia; Vasa, Srinivas; Pattipati, Ramesh; Valige, Ravindar; Kummari, Bhaskar; Pothukanuri, Srinivasu; De Piano, Cyntia; Morrissey, Ian; Holden, Kirsty; Warn, Peter; Marcoccia, Francesca; Benvenuti, Manuela; Pozzi, Cecilia; Tassone, Giusy; Mangani, Stefano; Docquier, Jean-Denis; Pallin, David; Elliot, Richard; Lemonnier, Marc; Everett, Martin [Journal of Medicinal Chemistry, 2020, vol. 63, # 24, p. 15802 - 15820]

78
(2S,5R)-2-(dichloromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one [ No CAS ]
[ 10534-59-5 ]
tetrabutylammonium (2S,5R)-2-(dichloromethyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	Stage #1: (2S,5R)-2-(dichloromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one With sulfur trioxide trimethylamine complex; triethylamine In dichloromethane at 0 - 20℃; for 4h; Inert atmosphere; Stage #2: With pyridine triethylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; Stage #3: tetrabutylammonium acetate In dichloromethane; water; N,N-dimethyl-formamide for 2h;	3.c c. Tetrabutylammonnium (2S,5R)-2-(dichloromethyl)-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate A solution of 2-(dichloromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one (85 mg, 0.37 mmol) in DCM (10 mL) was treated at 0°C with TEA (0.2 mL, 0.8 mmol) and sulfur trioxide pyridine complex (0.12g, 0.76 mmol). The mixture was stirred at room temperature for 4h then evaporated to dryness. The residue was redissolved in DMF (2 mL) and treated with TEA (0.4 mL, 1.6 mmol) and pyridine complex (0.12g, 0.76 mmol). The mixture was stirred at room temperature for 2h then a solution of n-tetrabutylammonium acetate (0.28g, 0.8 mmol) in water (10 mL) was added. After 2h, the mixture was diluted with DCM and the organic extract washed with water then brine, dried (Na2SO4) the evaporated to give an oil. This was chromatographed on silica eluting with 0-100% ethyl acetate in hexane then 6% methanol in DCM to afford a colourless oil (68 mg, 33%). M/z 304.4, 306.3 (M-)
33%	Stage #1: (2S,5R)-2-(dichloromethyl)-6-hydroxy-1,6-diazabicyclo[3.2.1]octan-7-one With sulfur trioxide pyridine complex; triethylamine In dichloromethane at 0℃; for 4h; Stage #2: tetrabutylammonium acetate In dichloromethane; water at 20℃; for 2h;

Reference： [1]Current Patent Assignee: ANTABIO SAS - EP3608318, 2020, A1 Location in patent: Paragraph 0080; 0110; 0115-0116
[2]Davies, David T.; Leiris, Simon; Zalacain, Magdalena; Sprynski, Nicolas; Castandet, Jérôme; Bousquet, Justine; Lozano, Clarisse; Llanos, Agustina; Alibaud, Laethitia; Vasa, Srinivas; Pattipati, Ramesh; Valige, Ravindar; Kummari, Bhaskar; Pothukanuri, Srinivasu; De Piano, Cyntia; Morrissey, Ian; Holden, Kirsty; Warn, Peter; Marcoccia, Francesca; Benvenuti, Manuela; Pozzi, Cecilia; Tassone, Giusy; Mangani, Stefano; Docquier, Jean-Denis; Pallin, David; Elliot, Richard; Lemonnier, Marc; Everett, Martin [Journal of Medicinal Chemistry, 2020, vol. 63, # 24, p. 15802 - 15820]

79
[ 10534-59-5 ]
tert-butyl 4-[(2R,5R)-6-(benzyloxy)-7-oxo-6-azabicyclo[3.2.1]octane-2-amido]piperidine-1-carboxylate [ No CAS ]
tetrabutylazanium (2R,5R)-2-({1-[(tert-butoxy)carbonyl]piperidin-4-yl}carbamoyl)-7-oxo-6-azabicyclo[3.2.1]octan-6-yl sulfate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: tert-butyl 4-[(2R,5R)-6-(benzyloxy)-7-oxo-6-azabicyclo[3.2.1]octane-2-amido]piperidine-1-carboxylate With α-picoline; hydrogen; palladium(II) hydroxide; sulfur trioxide trimethylamine complex In water; isopropyl alcohol at 30℃; Autoclave; Stage #2: tetrabutylammonium acetate In ethyl acetate at 30℃; for 4h;	16 Example 16: [(2S,5R)-2-(N-(1-tert-butoxycarbonylpiperidin-4-yl)aminocarbonyl)-7-oxo-1,6-diazabicyclo[3.2. 1] Preparation of oct-6-yl] tetra-n-butylammonium sulfate (V) To the autoclave, add 100 ml of isopropanol and 100 ml of water as solvents, and add 46.0 g (0.1 mol) of (2S,5R)-6-benzyloxy-N-(1-tert-butoxycarbonylpiperidine prepared in Example 15 -4-yl)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (IV), 2.3 g palladium hydroxide, 18.6 g (0.2 mol) 2-methyl Pyridine, 20.9 g (0.15 mol) of trimethylamine sulfide trioxide complex.Combined kettle, after nitrogen replacement three times, hydrogen replacement three times,Maintain the hydrogen pressure at 0.3 MPa and stir the reaction at 30°C until the reaction is complete by HPLC. Open the kettle after nitrogen replacement three times,The catalyst was filtered off by filtration, and the filter cake was washed with 20 g of water.The filtrate was washed with 200 g of ethyl acetate.45.2 g (0.15 mol) of tetra-n-butylammonium acetate was added to the aqueous phase, and the reaction was stirred at 30°C for 4 h. Add 200 grams of dichloromethane, stir and transfer to a separatory funnel, let stand for liquid separation. The aqueous phase was washed twice with dichloromethane, 80 g each time. The organic phases were combined, and after the solvent was distilled off under reduced pressure, 100 g of methyl isobutyl ketone was added and stirred. Cooled to 0 , crystallized. Filter with suction, wash with 40 g of methyl isobutyl ketone, and dry in vacuo to obtain 55.9 g of [(2S,5R)-2-(N-(1-tert-butoxycarbonylpiperidin-4-yl)aminocarbonyl)- 7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]tetra-n-butylammonium sulfate (V), white solid, HPLC purity 99.3%, yield 81.0%.

Reference： [1]Current Patent Assignee: XINFA PHARMACEUTICAL CO LTD - CN111072660, 2020, A Location in patent: Paragraph 0132-0133

80
[ 1192491-61-4 ]
[ 10534-59-5 ]
[ 1416134-53-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	In water at 20 - 25℃;	1 Example 1,([(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt(Compound B) Preparation Add purified water (2500ml) into the reaction flask, add crude product A-2 (500.0g, purity 99.9%), stir and dissolve at room temperature, tetrabutylammonium acetate 787.3g (1.5eq), stir for 1-2h, dichloromethane was added to the reaction solution for extraction twice, the dichloromethane layers were combined, dried over anhydrous sodium sulfate, filtered with suction, washed, and concentrated to obtain an oily substance. Acetone and ethyl acetate were added and stirred for crystallization, filtered with suction, washed, and dried to obtain 785.0 g of target compound B with a yield of 89.0% and a purity of 99.9%.

Reference： [1]Current Patent Assignee: QILU PHARMACEUTICAL GROUP CO LTD - CN111196807, 2020, A Location in patent: Paragraph 0046-0047

81
[ 1417788-76-1 ]
[ 10534-59-5 ]
methyl 4-O-acetyl-2,3-O-(2',3'-dimethoxybutane-2',3'-diyl)-α-L-quinovopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	Stage #1: methyl 2,3-O-(2',3'-dimethoxybutane-2',3'-diyl)-α-L-fucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at -40℃; for 7h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In toluene at 20℃; for 14h; Inert atmosphere;	3.13. Methyl 4-O-acetyl-2,3-O-(2',3'-dimethoxybutane-20,30-diyl)-α-L-quinovopyranoside (17) Compound 16 (6.09 g, 20.6 mmol) was placed under N2 and dissolved in dry CH2Cl2 (90 mL)and dry pyridine (14 mL). The solution was cooled to 40 °C and trifluoromethanesulfonic anhydride(4.2 mL, 25 mmol) was added. The reaction was stirred at 40 °C for 7 h, then allowed to reachroom temperature. The organic phase was washed with sat. NaHCO3 solution (100 mL) and brine(100 mL), dried over MgSO4, filtered and concentrated in vacuo. The dark red/brown oil obtained wasimmediately used in the next step.The crude and tetrabutylammonium acetate (7.55 g, 25.0 mmol) were placed under N2 and drytoluene (60 mL) was added. The reaction was stirred for 14 h at room temperature and the solvent wasthen removed under reduced pressure. The product was purified via flash chromatography on silicagel (cyclohexane/EtOAc, 4:11:1) to yield 17 a pale-yellow syrup (4.71 g, 68% over 2 steps). Rf = 0.7(cyclohexane/EtOAc, 1:1); [α]20D +47 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3) 4.80 (t, J = 9.7 Hz, 1H,H-4), 4.69 (d, J = 3.6 Hz, 1H, H-1), 4.06 (t, J = 9.7 Hz, 1H, H-3), 3.84-3.72 (m, 2H, H-2, H-5), 3.41 (s, 3H,OCH3), 3.24 (s, 3H, OCH3), 3.22 (s, 3H, OCH3), 2.07 (s, 3H, CH3(OAc)), 1.32 (s, 3H, CH3(BDA)), 1.24 (s,3H, CH3(BDA)), 1.17 (d, J = 6.3 Hz, 3H, H-6); 13C NMR (126 MHz, CDCl3) 169.9 (C=O), 100.0, 99.5(2 C(ketal)), 97.9 (C-1), 73.3 (C-4), 68.7 (C-2), 67.1 (C-3), 66.1 (C-5), 55.2, 48.0, 47.6 (3 OCH3), 21.0(CH3(OAc)), 17.9, 17.8 (2 CH3(BDA)), 17.5 (C-6); HRMS (ESI) m/z calculated for C15H26O8 [M + Na]+357.1525, found 357.1523.

Reference： [1]Guazzelli, Lorenzo; Oscarson, Stefan; Reihill, Mark; Remaut, Han [Molecules, 2020, vol. 25, # 18]

82
[ 10534-59-5 ]
benzyl [4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-(2,2,2-trichloroethoxy)carbonylamino-β-D-glucopyranoside [ No CAS ]
benzyl [2-O-acetyl-4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-mannopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-(2,2,2-trichloroethoxy)carbonylamino-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	Stage #1: benzyl [4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-(2,2,2-trichloroethoxy)carbonylamino-β-D-glucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0℃; Inert atmosphere; Stage #2: tetrabutylammonium acetate In toluene for 8h; Sonication; Inert atmosphere;	1 Benzyl [2-O-acetyl-4,6-O-benzylidine-3-O-p-methoxy-benzyl-b-D- mannopyranosyl]- (14)-3,6-di-O-benzyl-2-deoxy-2-(2,2,2- trichloroethoxy)carbonylamino-b-D-glucopyranoside S19. From S18: To a stirred solution of disaccharide S18 (1.02 g, 1.02 mmol, 1 equiv.) in anhydrous CH2Cl2 (13 mL) was added anhydrous pyridine (0.58 mL, 7.17 mmol, 7 equiv.), followed by dropwise addition of Tf2O (0.30 mL, 1.79 mmol, 1.75 equiv.) at 0 oC under argon. The reaction mixture was stirred at 0 oC until TLC indicated the disappearance of starting material (4 hrs). Upon completion, it was diluted with CH2Cl2 (20 mL), washed with 0.5N HCl (20 mL) and brine (10 mL). The separated organic layer was dried over MgSO4 and concentrated in vacuo. The crude residue was mixed with Bu4NOAc (927 mg, 3.07 mmol, 3 equiv.) and dissolved in toluene (20 mL). The solvent was removed in vacuo and the residue was co-evaporated with toluene twice; then, redissolved in anhydrous toluene (13 mL) and the mixture was sonicated for 8 h. During this time, we observed a partial deprotection of NHTroc and the reaction mixture was concentrated under high vacuum. The obtained residue was dissolved in CH2Cl2 (13 mL) and treated with NaHCO3 (430 mg, 5.12 mmol, 5 equiv.) and 2,2,2-trichloro ethyl chloroformate (0.71 mL, 5.12 mmol, 5 equiv.) at 0 oC under argon. After stirring for 3h, the reaction mixture was diluted with CH2Cl2 (20 mL), washed with water (20 mL) and brine (10 mL). The separated organic layer was dried over MgSO4 and concentrated in vacuo. The obtained residue was purified by silica gel column chromatography using EtOAc/toluene (1:5) as eluent to give compound S19 as a white powder (650 mg, 61%).

Reference： [1]Current Patent Assignee: ACADEMIA SINICA - WO2020/205034, 2020, A1 Location in patent: Page/Page column 13; 37; 39-40

83
benzyl [4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]
[ 10534-59-5 ]
benzyl [2-O-acetyl-4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-mannopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: benzyl [4,6-O-benzylidine-3-O-p-methoxybenzyl-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at 0℃; for 2h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In toluene for 8h; Sonication; Inert atmosphere;	1 Benzyl [2-O-acetyl-4,6-O-benzylidine-3-O-p-methoxy-benzyl-b-D- mannopyranosyl]-(14) -3,6-di-O-benzyl-2-deoxy-2-phthalimido-b-D-glucopyranoside S21. To a stirred solution of disaccharide S20 (936 mg, 0.985 mmol, 1 equiv.) in anhydrous CH2Cl2 (12 mL) was added anhydrous pyridine (0.56 mL, 6.90 mmol, 7 equiv.), then trifluoromethanesulfonic anhydride (0.29 mL, 1.72 mmol, 1.75 equiv.) was added dropwise at 0 oC under argon and the mixture was stirred at 0 oC until TLC indicated the disappearance of starting material (2 h). Upon completion, the reaction mixture was diluted with CH2Cl2 (20 mL), washed with 0.5 N HCl (20 mL) and brine (10 mL). The separated organic layer was dried over MgSO4, concentrated in vacuo and the obtained residue was used as is for further reactions. The above-obtained residue was added Bu4NOAc (594 mg, 1.97 mmol, 2 equiv.) and dissolved in toluene (18 mL). The solvent was removed in vacuo and the residue was co-evaporated with toluene twice to remove traces of water. The residue was redissolved in anhydrous toluene (12 mL) and the mixture was sonicated for 8 h. Upon completion, the reaction mixture was diluted with EtOAc (20 mL), washed with water (20 mL) and brine (10 mL). The separated organic layer was dried over MgSO4 and concentrated. The obtained residue was purified by silica gel column chromatography using EtOAc/hexane (1:2) as eluent to give compound S21 as white powder (913 mg, 93%). Rf = 0.29 (silica gel, EtOAc:hexane = 1:2); 1H NMR (600 MHz, CDCl3): d 7.76-7.49 (m, 4H, Ar-H), 7.48-7.46 (m, 2H, Ar-H), 7.39-7.31 (m, 7H, Ar-H), 7.26-7.22 (m, 3H, Ar-H), 7.10-7.06 (m, 1H, Ar-H), 7.04-7.03 (m, 4H, Ar-H), 6.99-6.98 (m, 2H, Ar-H), 6.90-6.84 (m, 5H, Ar-H), 5.49 (s, 1H, Ph- CH), 5.44 (d, J = 3.0 Hz, 1H), 5.09 (d, J = 7.8 Hz, 1H, C1-Hb), 4.82-4.76 (m, 3H), 4.68 (s, 1H, C1-Hb), 4.58 (d, J = 12.0 Hz, 1H), 4.49-4.44 (m, 3H), 4.38 (d, J = 12.6 Hz, 1H), 4.26- 4.19 (m, 2H), 4.17-4.11 (m, 2H), 3.86-3.82 (m, 2H), 3.78 (s, 3H, -CH3), 3.78-3.76 (m, 1H), 3.57-3.54 (m, 2H), 3.44 (dd, J = 10.2, 3.6 Hz, 1H), 3.13 (ddd, J = 9.6, 9.6, 4.8 Hz, 1H), 2.15 (s, 3H, -CH3); 13C NMR (150 MHz, CDCl3): d 170.2, 167.8, 159.2, 138.5, 137.8, 137.4, 137.1, 133.6, 131.5, 129.7, 129.2, 128.9, 128.5, 128.1, 128.1, 127.9, 127.9, 127.8, 127.7, 127.6, 127.5, 127.1, 126.0, 123.1, 113.8, 101.4, 99.5, 97.3, 79.1, 77.7, 76.9, 75.4, 74.5, 74.3, 73.5, 71.3, 70.7, 69.1, 68.4, 68.3, 66.9, 55.6, 55.2, 21.0; HRMS (ESI-TOF) m/e : Calcd for C58H57NO14Na [M+Na]+: 1014.3671 found 1014.3699.

Reference： [1]Current Patent Assignee: ACADEMIA SINICA - WO2020/205034, 2020, A1 Location in patent: Page/Page column 13; 37-38; 42-43

84
[ 10534-59-5 ]
[ 108-24-7 ]
[ 152961-70-1 ]
[ 152961-73-4 ]

Yield	Reaction Conditions	Operation in experiment
73%	In acetonitrile at 40℃; for 10h;	1 Synthesis of compound of formula 5: The compound of formula 4 (0.3 g, 1.33 mmol) was dissolved in anhydrous acetonitrile (3 ml) solvent, and the weighed tetrabutylammonium acetate (0.28 g, 0.93 mmol) was added to it,Then add acetic anhydride (0.19 ml, 1.99 mmol) to the above mixture,The temperature was raised to 40 C, and the reaction was stirred for 10 hours. TLC monitors the completion of the reaction,It was quenched with saturated aqueous sodium bicarbonate solution, extracted with ethyl acetate (3×10 mL), the organic phase was collected, and the product was separated and purified by column chromatography after distillation under reduced pressure (ethyl acetate: petroleum ether = 1:4).Finally, the eluate was concentrated to give a pale yellow oil 5 (0.26 g, yield 73%).

Reference： [1]Current Patent Assignee: SHANXI TUMOUR INST; SHANXI TUMOUR HOSPITAL - CN112608296, 2021, A Location in patent: Paragraph 0018; 0022; 0025

85
[ 10534-59-5 ]
dimethylthexylsilyl [4,6-O-benzylidene-3-O-(2-methylnaphthyl)-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]
dimethylthexylsilyl [2-O-acetyl-4,6-O-benzylidene-3-O-(2-methylnaphthyl)-β-D-mannopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: dimethylthexylsilyl [4,6-O-benzylidene-3-O-(2-methylnaphthyl)-β-D-glucopyranosyl]-(1→4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranoside With pyridine; trifluoromethylsulfonic anhydride In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: tetrabutylammonium acetate In toluene Inert atmosphere;

Reference： [1]Abrescia, Nicola G. A.; Ardá, Ana; Boons, Geert-Jan; Bunyatov, Mehman; Delgado, Sandra; Gagarinov, Ivan A.; Srivastava, Apoorva D.; Unione, Luca [Angewandte Chemie - International Edition, 2021, vol. 60, # 35, p. 19287 - 19296][Angew. Chem., 2021, vol. 133, # 35, p. 19436 - 19445]

86
[ 10534-59-5 ]
C₁₇H₁₃ClF₄INO₂ [ No CAS ]
C₁₉H₁₆F₄INO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In N,N-dimethyl-formamide at 80 - 90℃; for 2h;	7.7.2 Preparation of Intermediate 7-4 To a solution of Intermediate 7-3 (30 g, 60.0 mmol, 1.0 eq.) in DMF (300 mL) was added tetrabutylammonium acetate (90 g, 300 mmol, 5.0 eq.) in one portion. The resulting mixture was stirred at 80~90 °C for 2 hours. LCMS trace showed that the reaction was completed. The mixture was cooled to 20 °C and poured into water (1 L). The aqueous phase was extracted with ethyl acetate (500 mL X 3). The combined organic phase was washed with brine (500 mL X 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (SiO2, PE/EA=5/1) to give Intermediate 7-4 (28 g, 89% yield) was obtained as yellow oil. MS: m/z = 525.9 [M+H]+.
89%	In N,N-dimethyl-formamide at 80 - 90℃; for 2h;	7.7.2 Preparation of Intermediate 7-4 To a solution of Intermediate 7-3 (30 g, 60.0 mmol, 1.0 eq.) in DMF (300 mL) was added tetrabutylammonium acetate (90 g, 300 mmol, 5.0 eq.) in one portion. The resulting mixture was stirred at 80~90 °C for 2 hours. LCMS trace showed that the reaction was completed. The mixture was cooled to 20 °C and poured into water (1 L). The aqueous phase was extracted with ethyl acetate (500 mL X 3). The combined organic phase was washed with brine (500 mL X 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by silica gel chromatography (SiO2, PE/EA=5/1) to give Intermediate 7-4 (28 g, 89% yield) was obtained as yellow oil. MS: m/z = 525.9 [M+H]+.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0319; 0321-0322
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0319; 0321-0322

87
[ 10534-59-5 ]
C₁₇H₁₄F₄INO₂ [ No CAS ]
C₁₉H₁₇F₄NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.8%	In N,N-dimethyl-formamide at 100℃; for 4h;	1.1.17 Preparation of Intermediate 1-20 To a solution of Intermediate 1-19 (2.0 g, 4.28 mmol, 1.0 eq.) in DMF (20 mL) was added tetrabutylammonium acetate (5.16 g, 17.12 mmol, 4.0 eq.). The resulting mixture was stirred at 100 °C for 4 h. TLC showed the reaction was complete. The reaction mixture was partitioned between EA (100 mL) and water (100 mL). The organic phase was separated, and the aqueous was extracted with EA (50 mL X 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0~20% EA/PE gradient at 30mL/min) to give Intermediate 1-20 (1.50 g, 87.8% yield) as a pale brown oil
87.8%	In N,N-dimethyl-formamide at 100℃; for 4h;	1.1.17 Preparation of Intermediate 1-20 To a solution of Intermediate 1-19 (2.0 g, 4.28 mmol, 1.0 eq.) in DMF (20 mL) was added tetrabutylammonium acetate (5.16 g, 17.12 mmol, 4.0 eq.). The resulting mixture was stirred at 100 °C for 4 h. TLC showed the reaction was complete. The reaction mixture was partitioned between EA (100 mL) and water (100 mL). The organic phase was separated, and the aqueous was extracted with EA (50 mL X 2). The combined organic layers were washed with brine (50 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column (ISCO; 20 g SepaFlash Silica Flash Column, Eluent of 0~20% EA/PE gradient at 30mL/min) to give Intermediate 1-20 (1.50 g, 87.8% yield) as a pale brown oil

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0227; 0260-0261
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0227; 0260-0261

88
[ 10534-59-5 ]
C₁₅H₁₁Cl₂FINO [ No CAS ]
C₁₇H₁₄ClFINO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.15%	In N,N-dimethyl-formamide at 90℃; for 1.5h;	17.17.6 Preparation of Intermediate 17-8 To a solution of Intermediate 17-7 (18 g, 41.09 mmol, 1 eq.) in DMF (100 mL) was added TBAAc (61.94 g, 205.45 mmol, 62.57 mL, 5 eq.). The mixture was stirred at 90°C for 1.5 h. LCMS showed that the reaction was complete. The reaction was cooled to 20 °C and poured into water (100 mL). The aqueous phase was extracted with EA (100 mL X 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, PE/EA=10/1 to 5/1) to give Intermediate 17-8 (17.1 g, 90.15% yield) as a yellow oil. LCMS: ESI-MS: m/z 462.1 [M+H]+.
90.15%	In N,N-dimethyl-formamide at 90℃; for 1.5h;	17.17.6 Preparation of Intermediate 17-8 To a solution of Intermediate 17-7 (18 g, 41.09 mmol, 1 eq.) in DMF (100 mL) was added TBAAc (61.94 g, 205.45 mmol, 62.57 mL, 5 eq.). The mixture was stirred at 90°C for 1.5 h. LCMS showed that the reaction was complete. The reaction was cooled to 20 °C and poured into water (100 mL). The aqueous phase was extracted with EA (100 mL X 3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, PE/EA=10/1 to 5/1) to give Intermediate 17-8 (17.1 g, 90.15% yield) as a yellow oil. LCMS: ESI-MS: m/z 462.1 [M+H]+.

Reference： [1]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0398; 0408-0409
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - WO2021/198981, 2021, A1 Location in patent: Paragraph 0398; 0408-0409

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	10534-59-5	MDL No. :	MFCD00043208
Formula :	C₁₈H₃₉NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MCZDHTKJGDCTAE-UHFFFAOYSA-M
M.W :	301.51	Pubchem ID :	82707
Synonyms :	Tetra-n-butylammonium acetate

Num. heavy atoms :	21
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.94
Num. rotatable bonds :	12
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	92.96
TPSA :	40.13 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.83 cm/s

Log Po/w (iLOGP) :	-2.31
Log Po/w (XLOGP3) :	0.44
Log Po/w (WLOGP) :	3.76
Log Po/w (MLOGP) :	0.11
Log Po/w (SILICOS-IT) :	4.71
Consensus Log Po/w :	1.34

[ CAS No. 10534-59-5 ] {[proInfo.proName]}

Quality Control of [ 10534-59-5 ]

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Product Details of [ 10534-59-5 ]

Calculated chemistry of [ 10534-59-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 10534-59-5 ]

Application In Synthesis of [ 10534-59-5 ]

[ 10534-59-5 ] Synthesis Path-Upstream 1~4

[ 10534-59-5 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

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Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	1.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.19
Solubility :	19.3 mg/ml ; 0.0639 mol/l
Class :	Very soluble
Log S (Ali) :	-0.85
Solubility :	42.5 mg/ml ; 0.141 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-6.35
Solubility :	0.000135 mg/ml ; 0.000000449 mol/l
Class :	Poorly soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.96

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P271-P280-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Yield	Reaction Conditions	Operation in experiment
99.1%	at 115℃; for 7 h;	Example 8 - Preparation of tert-butyl 2-[(4R,6S)-2,2-dimethyl-6-[(rnethyl- carbonyloxy)methyl]-1 ,3-dioxan-4-yl]acetate from tetra-n-butyl ammonium acetateIn a 100ml_ round vessel was added crude tert-butyl 2-[(4R,6S)-6-(chloromethyl)- 2,2-dimethyl-1 ,3-dioxan-4-yl]acetate (5.0g) and tetra-n-butyl ammonium acetate (4.3g). The mixture was heated to 115°C and became liquid at ~50°C. The mixture was heated for 7 hours.Heptane (15mL) was added to the reaction and the mixture stirred for 5 minutes at 70°C before decanting the heptane phase. The mixture was further extracted with heptane (2 x 10ml_) at 70°C. The combined heptane extracts were washed with water (10mL) and then filtered through a bed of celite filter aid. The heptane filtrate was partially evaporated then cooled to -10°C. The pale yellow crystals were filtered and dried, yield = 1.1g with a purity of 99.1 percent by HPLC.
7.2 g	at 25 - 95℃; for 24 h;	To a solution of ieri-butyl 2-((4R,6S)-6-(chloromethyl)-2,2-dimethyl-l,3-dioxan-4- yl)acetate (10 g) in NMP (300 mL) was added tetra butyl ammonium acetate (30 g) at 25°C. Resulting reaction mixture was heated to 95°C and stirred for 24 h. After cooling to room temperature, water (450 mL) was added and then extracted with n-heptane (3 X 150 mL). To the combined organic layer was added activated charcoal (1 g) and stirred for 5 h, filtered the activated charcoal and filtrate was concentrated to obtained crude product, which was further recrystallized from n-heptane to obtain off white solid material (7.2g, 99.2percent GC purity and 99.5percent de). Gas Chromatographic system: Instrument : Gas Chromatograph equipped with FID detector. Column : DB-5, length: 30 mtr. , Dia.: 0.53mm, 5.0μιη Capillary Column. Detector : Flame Ionization Detector. Carrier gas : Nitrogen. Gas Chromatograph parameters: Carrier gas pressure : 8.0 psi. Detector Temperature : 280°C Injector Temperature : 280°C Injection volume Split ratio Retention time: Approximate retention time for compound [XI] is about 12.0 min

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