Name: 1774-47-6|Trimethylsulfoxonium iodide|98%
Brand: Ambeed
SKU: A108841
Price: 6.0 USD
Availability: InStock
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1
[ 110-86-1 ]
[ 1774-47-6 ]
[ 930-73-4 ]

Reference： [1]Justus Liebigs Annalen der Chemie,1958,vol. 611,p. 117,120

2
[ 24686-78-0 ]
[ 1774-47-6 ]
[ 34259-94-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With sodium hydride; In dimethyl sulfoxide; at 20 - 65℃; for 3h;	1-Oxa-6-aza-spiro[2.5]oct-6-yl-phenyl-methanone (A4) was synthesized according to literature (Vacher et al. J Med Chem, (1999), 42, 1648). In detail, 19.6 g (490 mmol) NaH (60percent in oil) was suspended in 600 ml DMSO and stirred at 65° C for 2 hrs. After cooling to room temperature 108 g (490 mmol) trimethylsulfoxonium iodide was added and the mixture was stirred for 15 min at room temperature. Then, 95 g (470 mmol) 1- benzoylpiperidin-4-one dissolved in 300 ml DMSO was added to the mixture and the solution was stirred for 45 min. The reaction mixture was poured in water and extracted with ethyl acetate for three times. The combined organic layers were washed with water and brine, dried over Na2SO4 and evaporated in vacuo to yield the product. Yield: 84 g (83 percent) yellow oil.MS (APCI): m/z 218 (M+1)*. 1H NMR (CDCI8, 600 MHz) delta (ppm): 1.35-1.60 (m, 2H, piperidine); 1.76-2.68 (m, 2H, piperidine); 2.74 (bs, 2H1 oxirane); 3.43-3.72 (m, 3H, prperidine); 4.18-4.36 (m, 1H, piperidine); 7.37-7.46 (m, 5H, phenyl).
54%		Trimethylsulfoxonium iodide (11.2 g, 51.0 mmol), dimethyl sulfoxide (15 mE) and sodium hydride (60percent in mineral oil, 157 mg, 6.54 mmol) were added to a 50-mE round-bottom flask fitted with a magnetic stit The resulting mixture was stirred for 30 mm at room temperature. 1-ben- zoylpiperidin-4-one (500 mg, 2.18 mmol) was added and the resulting solution was stirred at room temperature for 4 h. The reaction was quenched by the addition of water (30 mE) and extracted with dichloromethane (3x30 mE). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The residue was purified by colunm chromatography using ethyl acetate to afford phenyl(1 -oxa-6-azaspiro[2.5]octan-6-yl)methanone (Intermediate 2-36, 2.00 g, 54percent). LCMS: (ESI) mlz 218 [M+H].

Reference： [1]Patent: WO2009/60030,2009,A1 .Location in patent: Page/Page column 34-35
[2]Journal of Medicinal Chemistry,2010,vol. 53,p. 7167 - 7179
[3]Patent: US2016/185785,2016,A1 .Location in patent: Paragraph 2074; 2075
[4]Canadian Journal of Chemistry,1971,vol. 49,p. 3075 - 3085

3
[ 20026-96-4 ]
[ 1774-47-6 ]
[ 19966-66-6 ]

Reference： [1]Chemical and pharmaceutical bulletin,1968,vol. 16,p. 784 - 792

4
[ 288-88-0 ]
[ 1774-47-6 ]
[ 86404-63-9 ]
[ 86386-73-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,1993,vol. 30,p. 1405 - 1412

5
[ 1774-47-6 ]
[ 141-05-9 ]
[ 710-43-0 ]
[ 3999-55-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1983,p. 2921 - 2926
[2]Journal of the Chemical Society. Perkin transactions I,1983,p. 2921 - 2926

6
[ 2979-69-3 ]
[ 1774-47-6 ]
[ 128405-66-3 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1990,p. 689 - 693

7
[ 5232-99-5 ]
[ 1774-47-6 ]
[ 31002-34-3 ]

Reference： [1]Journal of the American Chemical Society,1989,vol. 111,p. 7866 - 7872

8
[ 1774-47-6 ]
[ 81926-14-9 ]
[ 81926-24-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1982,p. 841 - 848

9
[ 1774-47-6 ]
[ 81990-97-8 ]
[ 938-85-2 ]
[ 73-40-5 ]
[ 578-76-7 ]
[ 2958-98-7 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1983,vol. 31,p. 861 - 869

10
[ 1774-47-6 ]
[ 81980-39-4 ]
[ 938-85-2 ]
[ 73-40-5 ]
[ 578-76-7 ]
[ 69-89-6 ]
[ 2958-98-7 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1983,vol. 31,p. 861 - 869

11
[ 1774-47-6 ]
[ 623-91-6 ]
[ 710-43-0 ]
[ 3999-55-1 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1983,p. 2921 - 2926
[2]Journal of the Chemical Society. Perkin transactions I,1983,p. 2921 - 2926

12
[ 1885-38-7 ]
[ 1774-47-6 ]
[ 4660-02-0 ]

Reference： [1]Organometallics,2019,vol. 38,p. 2582 - 2589
[2]Journal of Medicinal Chemistry,1977,vol. 20,p. 771 - 776

13
[ 1885-38-7 ]
[ 1774-47-6 ]
[ 4660-02-0 ]
[ 4660-02-0 ]

Reference： [1]Journal of Medicinal Chemistry,1977,vol. 20,p. 771 - 776

14
[ 1016-78-0 ]
[ 1774-47-6 ]
[ 124-40-3 ]
(1R,2S)-1-(3-Chloro-phenyl)-3-dimethylamino-1-phenyl-propan-2-ol [ No CAS ]
(1R,2R)-1-(3-Chloro-phenyl)-3-dimethylamino-1-phenyl-propan-2-ol [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1979,vol. 22,p. 1373 - 1379

15
[ 488-10-8 ]
[ 1774-47-6 ]
5-methyl-1-(pent-2'-enyl)bicyclo<3.1.0>hexan-2-one [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1996,vol. 61,p. 8885 - 8896

16
[ 14736-31-3 ]
[ 1774-47-6 ]
2-Oxo-1a,2-dihydro-1H-7-oxa-cyclopropa[b]naphthalene-7a-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1996,vol. 6,p. 763 - 766

17
[ 86-57-7 ]
[ 1774-47-6 ]
[ 881-03-8 ]

Reference： [1]Polish Journal of Chemistry,1998,vol. 72,p. 2384 - 2388
[2]Organic Letters,2019,vol. 21,p. 9320 - 9325

18
[ 1774-47-6 ]
[ 5034-06-0 ]

Yield	Reaction Conditions	Operation in experiment
	With water; chlorine; at 50℃;	According to the literature method [Major R Tet. Al., J. Org. Chem. 23 (5): 1563-1565, 1958] preparation: Dimethyl sulfoxide and iodomethane were refluxed under N2 to give trimethoxythiodide iodide; Methoxythio iodide and chlorine reaction of trimethoxy sulfur chloride.

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 3636 - 3646
[2]Journal of Polymer Science, Part A: Polymer Chemistry,2019,vol. 57,p. 2450 - 2456
[3]Patent: CN106518812,2017,A .Location in patent: Paragraph 0064; 0065; 0066; 0067

19
[ 7535-56-0 ]
[ 1774-47-6 ]
[ 400611-25-8 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 1629 - 1633

20
[ 1885-38-7 ]
[ 1774-47-6 ]
(+/-)-cis-2-phenylcyclopropanecarbonitrile [ No CAS ]
(+/-)-trans-2-phenylcyclopropanecarbonitrile [ No CAS ]

Reference： [1]New Journal of Chemistry,2002,vol. 26,p. 1575 - 1583

21
[ 1774-47-6 ]
[ 50606-58-1 ]
[ 97267-35-1 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In acetonitrile; at 50℃; for 2.5h;	Ground 85% potassium hydroxide (5.2 g) was added to a suspension of <strong>[50606-58-1]1-benzyl-3-piperidone hydrochloride</strong> hydrate (5.0 g) and trimethylsulfoxonium iodide (5.3 g) in anhydrous acetonitrile (220 mL), followed by stirring at 50C under nitrogen atmosphere for two and half hours. After cooling to room temperature, insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was mixed with ethyl acetate (100 mL) and water (50 mL) and was separated. The organic layer was sequentially washed with water (50 mL) and brine (50 mL) and was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to yield the titled compound (4.07 g) as an oil.

Reference： [1]Patent: EP1568688,2005,A1 .Location in patent: Page/Page column 34

22
[ 13698-49-2 ]
[ 1774-47-6 ]
[ 427-51-0 ]

Yield	Reaction Conditions	Operation in experiment
51.51%		1.2 g of trimethyl sulfoxonium iodide (5.6 mmol) and 0.08 g of sodium hydride (3.3 mmol) were dissolved in 10 ml dimethylsulfoxide (DMSO) and stirred for 30 minutes at 5C under nitrogen gas. Then, 0.5 g of delmadinone acetate (1.24 mmole) were added and stirred for 5 hours. The mixture was allowed to room temperature for 24 hours. The mixture as poured into 1 N HCI (with ice) solution, the precipitate filtered and washed with water. Recrystallisation from isopropylether gave white powder of cyproterone acetate. * % yield = 51.51 from 0.5 g of starting materials.

Reference： [1]Patent: EP1359154,2003,A1 .Location in patent: Page/Page column 3; 20; 30

23
[ 3731-38-2 ]
[ 1774-47-6 ]
[ 122-94-1 ]
[ 160126-76-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; toluene;	EXAMPLE 1 A solution of sodium hydroxide (8.8 g) in water (90 ml) was added to a stirred mixture of quinuclidin-3-one (9.2 g), 4-butoxyphenol (12.2 g) and trimethylsulphoxonium iodide (32.4 g) in toluene (150 ml). The mixture was stirred at room temperature for 64 hours under an atmosphere of argon. The mixture was extracted with ethyl acetate (4100 ml). The ethyl acetate extracts were combined, washed with 2M sodium hydroxide solution (250 ml), water (250 ml) and then extracted with 2M hydrochloric acid (335 ml). The acidic extracts were combined, cooled to 5 C. and then basified by the addition of 11M sodium hydroxide solution (25 ml). The aqueous mixture was extracted with ethyl acetate (4*70 ml) and the ethyl acetate extracts were combined, washed with saturated brine (50 ml), dried (Na2 SO4) and evaporated. The residue was purified by flash column chromatography on silica gel (2 g, Merck 7736) to give 3-(4-butoxyphenoxymethyl)-3-hydroxyquinuclidine (1.5 g) as a colourless solid, m.p. 110-112 C.; microanalysis, found: C, 70.7; H, 9.0; N, 4.7%; C18 H27 NO3 requires: C,70.8; H, 8.9; N, 4.6%; NMR (CDCl3): 1.0(3H, t), 1.2-1.8(7H, m), 2.1(2H, m), 1.8-2.6(1H, br), 2.6-3.1(6H, m), 3.9(2H, t), 4.0(1H, d), 3.8(1H, d) and 6.8(4H, br s); m/z 306 (M+H).

Reference： [1]Patent: US5691349,1997,A

24
[ 14891-10-2 ]
[ 1774-47-6 ]
[ 125033-33-2 ]

Yield	Reaction Conditions	Operation in experiment
	In diethyl ether; dimethyl sulfoxide; paraffin oil;	a) Ethyl 5-aza-1- oxaspiro[2,4]heptane-5-carboxylate 23.5 g (107 mmol) of trimethylsulphoxonium iodide and 3.3 g of sodium hydride (80% strength in paraffin oil) are initially introduced and 80 ml of absolute dimethyl sulphoxide are added dropwise at 10 C. The mixture is stirred for an hour at room temperature and 15.7 g (100 mmol) of ethyl 3-oxopyrrolidine-1-carboxylate [J. Med. Pharm. Chem. 5, 752 (1962] in 20 ml of absolute dimethyl sulphoxide are then added dropwise in the course of 15 minutes. The mixture is stirred for one hour at room temperature, poured onto a mixture of ice and saturated sodium chloride solution and extracted using diethyl ether. The ether solutions are washed with sodium chloride solution, dried over Na2 SO4, concentrated and distilled. Yield: 6 g Boiling point: 80 C./0.15 mbar

Reference： [1]Patent: US5173484,1992,A

25
[ 1016-78-0 ]
[ 1774-47-6 ]
2-(3-Chlorophenyl)-2-phenyl oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With NaH; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dimethyl sulfoxide; mineral oil;	Step F Preparation of 2-(3-Chlorophenyl)-2-phenyl oxirane A 250 mL-round bottom flask was charged with NaH (60% dispersion in mineral oil) (1.92 g, 0.048 mol), washed with petroleum ether, then treated with dry DMSO (40 mL) under N2. To this reaction mixture was added trimethylsulfoxonium iodide (10.56 g, 0.048 mol) through a solid addition funnel over 15 min. After stirring for 0.5 hr, a solution of <strong>[1016-78-0]3-chlorobenzophenone</strong> (8.66 g, 0.04 mol) in DMSO (15 mL) was added dropwise, and the mixture was heated at 55 C. for 2 hr. The mixture was added to ice-water, extracted with ether (3*100 mL), the organics combined, dried (MgSO4), filtered, and concentrated to give the title compound.

Reference： [1]Patent: US5817678,1998,A

26
[ 37951-49-8 ]
[ 1774-47-6 ]
2-Ethyl-2-(3-methoxyphenyl)-oxiran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; dimethyl sulfoxide;	EXAMPLE 1 2-Ethyl-2-(3-methoxyphenyl) oxiran A solution of trimethylsulphoxonium iodide (88.3 g; 0.4 mole) in dry dimethylsulphoxide (500 ml) was slowly added to sodium hydride (9.6 g; 0.4 mole) in an atmosphere of nitrogen, with vigorous stirring, the temperature not being allowed to exceed 10 C. After two hours, evolution of hydrogen was essentially complete. Maintaining the temperature, the grey mixture was treated with suspension of <strong>[37951-49-8]3-methoxypropiophenone</strong> (48 g; 0.293 mole) in dry dimethylsulphoxide (100 ml). The mixture was stirred at ambient temperature for 11/2 hours, and then at 50 C. for 1 hour. The cooled mixture was treated with water (250 ml), and then shaken with two portions of ether (400 ml). The ether layers were washed with water and dried over magnesium sulphate, giving a residual 67 g of 90% pure epoxide title compound. Distillation gave 31 g of title compound bp (1 mm) 80-86 C.

Reference： [1]Patent: US4360519,1982,A

27
[ 27829-72-7 ]
[ 1774-47-6 ]
[ 59739-10-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In ice-water; dimethyl sulfoxide;	(1) Ethyl 2,3-methanohexanoate 15.6 g. of sodium hydride (content 65.1percent, 0.423 mol) were suspended in 800 ml. of dimethyl sulphoxide, and there were added, with stirring, 154 g. (0.7 mol) of trimethyloxosulphonium iodide in small portions at 20° to 30°C. over a period of 20 minutes. An exothermic reaction took place with the evolution of hydrogen. After stirring for 10 minutes, there was added, dropwise, a solution of 60 g. (0.423 mol) of ethyl hex-trans-2-enoate in 70 ml. of dimethyl sulphoxide at 20° to 30°C. The reaction mixture was stirred at 40°C. for 3 hours and then poured into 2 litres of ice-water and extracted with diethyl ether. The aqueous layer was treated with 60 ml. of concentrated hydrochloric acid and extracted with diethyl ether. The combined ethereal layer was washed with water, dried with magnesium sulphate and concentrated under reduced pressure. Distillation of the crude product gave 23.2 g. of ethyl 2,3 -methanohexanoate having the following physical characteristics:- b.p. 57° to 60°C./6 mm.Hg; NMR (CDCl3 and CCl4 solution); delta: 4.05 (2H, q), 0.95 (3H, t) and 0.70-0.48 (2H, dd); IR (liquid film); nu: 2950, 1720, 1450, 1405, 1370, 1330, 1265, 1200, 1180, 1100, 1040, 860 cm-1.

Reference： [1]Patent: US3978229,1976,A

28
CP [ No CAS ]
[ 1774-47-6 ]
[ 5034-06-0 ]
dimethyloxosulfonium methylide [ No CAS ]
sodium chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; In tetrahydrofuran; hexane; dimethyl sulfoxide;	EXAMPLE 13 To 10.2 ml (16.5 mM) of 15percent solution of n-butyllithium in n-hexane, 15 ml of n-hexane, 3.81 g (17.25 mM) of trimethylsulfoxonium iodide and 30 ml of DMSO were added and the mixture was stirred for 30 minutes. This reaction mixture was poured dropwise into a solution of 1.86 g (15 mM) of CP in 15 ml of DMSO in 4 hours. After reacting for two hours at room temperature, the treatments were carried out as described in Example 8. 1.29 g (62percent yield) of a primary product were produced, from which 0.87 g (43percent yield) of sabina ketone were obtained by distillation. Then, 12.85 g (100 mM) of <strong>[5034-06-0]trimethylsulfoxonium chloride</strong> and 150 ml of THF were added to 2.64 g (110 mM) of sodiumm hydride and the mixture was heated under reflux for 4 hours with stirring. After the reaction mixture was cooled, the by-produced sodium chloride was filtered off by using celite as filter aid. A THF solution of dimethylsulfoxonium methylide was obtained. This solution was supplemented to an amount of 200 ml by adding further THF and was stored in a refrigerator under nitrogen atmosphere.

Reference： [1]Patent: US4162258,1979,A

29
[ 1885-38-7 ]
[ 1774-47-6 ]
[ 4660-02-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In hexane; dimethyl sulfoxide;	EXAMPLE B Preparation of 2-phenyl-cyclopropanecarbonitrile To a dry 500 ml multi-neck round bottom flask fitted with an air stirrer, nitrogen inlet condenser and an addition funnel, 5 g of 60% sodium hydride (NaH), 10 ml of hexane, 100 ml of dimethyl sufoxide (DMSO) and 25 g of trimethyloxosulphonioum iodide ((CH3)3SOI) was added and stirred. To the resulting mixture there was added 12.9 g of 2-phenyl-acrylonitrile. The mixture was aged overnight. In the morning to the mixture was added 100 ml of methyl butyl ether, the mixture was quenched with 250 ml of water, stirred and allowed to settle. The organic layer was separated. To the aqueous layer 50 ml of methyl butyl ether was added, the mixture was stirred and allowed to settle. The organic layer was separated. The organic layers were combined and washed with 2×200 ml portions of brine. The gas chromatography test indicated that 59.6% of the starting material converted into 2-phenyl-cyclopropanecarbonitrile. The NMR spectrum of the 2-phenyl-cyclopropanecarbonitrile is as follows: 1.4 ppm (m, 1H); 1.5 ppm (m, 1H); 1.6 ppm (m, 1H); 2.7 ppm (m, 1H); 7.1 ppm (s, 2H); 7.3 ppm (d, 2H).

Reference： [1]Patent: US2006/287204,2006,A1 .Location in patent: Page/Page column 3

30
[ 2549-87-3 ]
[ 1774-47-6 ]
[ 1018669-01-6 ]

Reference： [1]Tetrahedron,2008,vol. 64,p. 2586 - 2595

31
[ 1774-47-6 ]
[ 115974-97-5 ]
[ 1057107-39-7 ]

Yield	Reaction Conditions	Operation in experiment
		2.2 eq NaH (60% dispersion in oil) and 2.5 eq trimethylsulfoxonium iodide were weighed into a dry flask under nitrogen. 20 ml anhydrous DMSO was added and the reaction stirred one hour at room temperature. The intermediate acid E117b (6.8 mmol), dissolved in 6 ml anhydrous DMSO was added dropwise. After 2.5 hours at room temperature, the reaction was poured into 1N HCl and extracted with EtOAc. The combined organic layers were washed with a minimal amount of aqueous sodium thiosulfate then brine. The combined organic layers were then dried over MgSO4, filtered and concentrated to provide the intermediate cyclopropane E117c. The material E117c was used without further purification.

Reference： [1]Patent: US2008/167340,2008,A1 .Location in patent: Page/Page column 17

32
[ 17159-79-4 ]
[ 1774-47-6 ]
[ 171361-65-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Product distribution / selectivity;	Intermediate 9; Ethyl 1 -oxaspiror2.51octane-6-carboxylate; Procedure 9a; To a mixture of trimethylsulfoxonium iodide and potassium tert-butoxide (as reported in Synthetic Communications, 33(12), 2135-2143; 3.9 g, 11.76 mmol) was added a solution of ethyl 4-oxocyclohexanecarboxylate (1 g, 5.87 mmol, Aldrich) in DMSO (20ml). The mixture was left to stir overnight at room temperature. The mixture was poured into water and extracted with diethyl ether; the organic phase was dried on Na2SO4, filtered and evaporated in vacuo to afford the title compound (704.5 mg, 65%), which was used without purification.Another batch of the same compound prepared using an analogous method showed the following NMR spectra:1H NMR (400 MHz, CDCI3): delta 4.06 (2H, q), 2.49-2.59 (2H, m), 2.26-2.28 (1 H, m), 1.63- 2.04 (6H, m), 1.27-1.49 (2H, m), 1.20 (3H, t) cis/trans 65:35
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Product distribution / selectivity;	Intermediate delta: Ethyl 1-oxaspiror2.5loctane-6-carboxylate; To a mixture of trimethylsulfoxonium iodide and potassium tert-butoxide (as reported in Synthetic Communications, 33(12), 2135-2143; 3.9 g, 11.76 mmol) was added a solution of ethyl 4-oxocyclohexanecarboxylate (1 g, 5.87 mmole, Aldrich) in DMSO (20 ml). The mixture was left to stir overnight at room temperature. The mixture was poured into water and extracted with diethyl ether; the organic phase was dried on Na2SO4, filtered and evaporated in vacuo to afford ethyl 1-oxaspiro[2.5]octane-6-carboxylate (704.5 mg, 65%), which was used without purification. Another batch of the same compound prepared using an analogous method gave 1 H-NMR (400 MHz, CDCI3): delta 1.20 (t, 3 H), 1.27-1.49 (m, 2 H), 1.63-2.04 (m, 6 H), 2.26-2.28 (m, 1 H), 2.49-2.59 (m, 2 H), 4.06 (q, 2 H).

Reference： [1]Patent: WO2008/92887,2008,A1 .Location in patent: Page/Page column 28
[2]Patent: WO2008/129007,2008,A1 .Location in patent: Page/Page column 32

33
[ 6971-74-0 ]
[ 1774-47-6 ]
[ 10533-83-2 ]

Reference： [1]Synthetic Communications,2008,vol. 38,p. 3074 - 3081

34
[ 1709-52-0 ]
[ 1774-47-6 ]
[ 1709-59-7 ]

Reference： [1]Synthetic Communications,2008,vol. 38,p. 3074 - 3081

35
[ 1774-47-6 ]
[ 130753-13-8 ]
benzyl 8H-spiro[8-azabicyclo[3.2.1]octane-3,2'-oxirane]-8-carboxylate [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 9016 - 9021

36
[ 519028-33-2 ]
[ 1774-47-6 ]
{1-[4-(4-fluoro-benzylcarbamoyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl]-1-methyl-ethyl}carbamic acid benzyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With magnesium hydroxide; In 1-methyl-pyrrolidin-2-one; water; at 97 - 109℃; for 6.5h;	NMP (-1.73 mL per gram of 2) was charged at 20-250C to a jacketed glass reactor equipped with a mechanical overhead stirrer, a thermocouple probe, and a condenser.Compound 2 (1 eq.), Mg(OH)2 (2 eqs.), Me3SO+I- (2 eqs.), and water (0.6 eq. ) were then added sequentially to the reactor while maintaining the temperature at 20-250C, after which the resulting mixture was degassed by passage of nitrogen through the head space of the agitated mixture for 5 minutes at 300C. Upon completion of the degassing, the nitrogen source to the reaction flask was disconnected and the reaction vented through the condenser to nitrogen. The mixture was then warmed to 97C over 1.5 hours, wherein an exotherm was observed when the temperature reached 97C causing the temperature to rise to about 1090C. The mixture was maintained at 97-1020C for 5 hours. The mixture was then cooled to 26C and degassed methanol (-1.73 mL per gram of 2) was added, followed by the addition of 5 N aqueous HCl (-0.86 mL per gram of 2). The mixture was then aged for 30 minutes, after which an aqueous solution of NaHSOs (0-03 eq.) was added. Seed crystals of compound 3 were then added.(Note: Crystallization would occur without seed, but seeding provides a more reliable method of crystal growth.) The mixture was aged for 1 hour at 36-400C5 and then degassed 5 N aqueous HCl (0.86 mL per gram of 2) was added. The mixture was cooled to 100C, aqueous NaHStheta3 (0.03 eq.) was added, and the mixture gradually cooled to 100C, after which the slurry was filtered and the resulting filter cake was washed with a 1 : 1 methanol: water mixture. The white granular crystalline product was dried to a constant weight under a stream of nitrogen to give compound 3 (99 wt% purity by HPLC assay), 89% overall yield (corrected for purity). Compound 3: (Spectra acquired at 0C-major carbamate rotamer reported) lH NMR (600.13 MHz, CDCI3) delta 11.95 (s, IH), 7.83 (t, J=6.0 Hz, IH), 7.36-7.28(overlapping m, 7H), 7.07-7.03 (m, 2H), 5.42 (s, IH), 5.00 (s, 2H), 4.57 (d, J=6.0 Hz, 2H), 3.65(s5 3H), 1.67 (s, 6H)13c NMR (150.92 MHz, CDCI3) delta 168.5, 162.4 (d, JcF=246.0 Hz), 159.8, 154.5, 151.1, 146.7, 135.9, 133.1 (d, JcF=3.1 Hz), 129.6 (d, JCF=7.9 Hz), 128.8, 128.7, 128.4, 124.4, 115.9 (d, JCF=21.4 Hz), 67.2, 57.3, 42.5, 33.1, 28.1.

Reference： [1]Patent: WO2009/88729,2009,A1 .Location in patent: Page/Page column 45
[2]Organic process research and development,2011,vol. 15,p. 73 - 83

37
[ 13482-23-0 ]
[ 1774-47-6 ]
cis-6-methoxy-1-oxaspiro[2,5]octane [ No CAS ]
trans-6-methoxy-1-oxaspiro[2,5]octane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%; 5%		Example 8 5-CHLORO-N-(t (CIS-l-HYDROXY-4-METHOXYCYCLOHEXYL) METHYLlPIPEltI DIN-4-YLTMETHYL)-1-ISOPROPYL-6-METHYL-2-OXO-1, 2-DIHYDROPYRIDINE-3-C ARBOXAMIDE; 8 (1) 6-Methoxy-l-oxaspirof2. 51octane; 0 + O O O (cis) (trans) To a stirred suspension of sodium hydride (60% in mineral oil, 1.20 g, 30.0 mmol) in dimethylsulfoxide (19 mL) was added trimethylsulfoxonium iodide (6.89 g, 31.3 mmol) at room temperature, and the mixture was stirred at room temperature for 30 min. To this mixture was added a solution of <strong>[13482-23-0]4-methoxycyclohexanone</strong> (3.53 g, 10.0 mmol, prepared according to Shvily, Ronit et al., J. Chem. Soc. Perkin Trans. 2,1997, 6, 1221) in dimethylsulfoxide (95 mL) dropwise at room temperature, and the mixture was stirred at room temperature for 20 h. Then the mixture was diluted with water (1.0 L), and extracted with diethyl ether (200 mL x 6). The combined organic layers were dried over magnesium sulfate, and concentrated in vacuo. The residue was chromatographed on a column of silica gel eluting n-hexane/ethyl acetate (v/v=15/1~10/1) to give 338 mg (9%, cis) and 204 mg (5%, trans) of the title compound as colorless oil respectively. (cis) 1H-NMR (CDCl3) 8 : 3.37 (3 H, s), 3.36-3. 28 (1 H, m), 2.65 (2 H, s), 1.95-1. 88 (2 H, m), 1.81-1. 55 (6 H, m). (trans) 1H-NMR (CDC13) 5 : 3.46-3. 40 (1 H, m), 3. 36 (3 H, s), 2.64 (2 H, s), 1.99-1. 91 (2 H, m), 1.85-1. 67 (4 H, m), 1.48-1. 39 (2 H, m).

Reference： [1]Patent: WO2005/73222,2005,A1 .Location in patent: Page/Page column 43

38
[ 1774-47-6 ]
[ 149506-79-6 ]
[ 1202411-57-1 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 36 Dibenzyl-(1 -oxa-spiro[2.5]oct-6-yl)-amine <n="223"/> Sodium hydride (2.121 g, 53.0 mmol) and trimethylsulfoxonium iodide (1 1.21 g, 50.9 mmol) were stirred in dimethylsulphoxide (100 ml) at room temperature for 1 hour. A solution of 4- (dibenzylamino)cyclohexanone (12.45 g, 42.4 mmol) in 50 ml dimethylsulfoxide was then added dropwise and stirring was continued for 1 hour. Ethyl acetate (200 ml) and water (100 ml) were added and the phases were separated. The organic layer was washed with water and brine, dried over Na2SC>4 and evaporated to dryness. This yielded 12.96 g of a light orange oil, which crystallized on standing and was purified by flash column chromatography on silica, eluting with a gradient of heptane:ethyl acetate 95:5 to 85:15 by volume, to yield 4.213 g of the title compound as a white solid. LRMS: m/z 307 [M+].

Reference： [1]Patent: WO2009/153720,2009,A1 .Location in patent: Page/Page column 220-221

39
[ 1774-47-6 ]
[ 89694-10-0 ]
[ 1188407-29-5 ]

Yield	Reaction Conditions	Operation in experiment
41%		Dimethyl sulfoxide (35 mL) was added to a dry round-bottomed flask containing NaH (1.82 g, 45.5 mmol, 60% in mineral oil). The resulting suspension was heated at 70 C. for 35 min during which time the suspension became a solution. The reaction mixture was cooled to room temperature, trimethylsulfoxonium iodide (10.0 g, 45.5 mmol) was added, and the mixture was stirred at room temperature for 30 min. 2-Methoxy-3-methyl-5-nitropyridine (4.50 g, 26.80 mmol) was added and the resulting dark red solution was stirred at room temperature for 30 min, at which time TLC showed complete consumption of starting material. The reaction mixture was transferred to a separatory funnel containing water (30 mL), and the aqueous layer was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by MPLC (silica gel, 20% ethyl acetate in hexanes) to afford 2-methoxy-3,6-dimethyl-5-nitropyridine (2.00 g, 41% yield) as a colorless solid identical to that prepared by the previous method: mp 85.5-86.2 C.; 1H NMR (400 MHz, CDCl3) delta 8.08 (s, 1H), 4.02 (s, 3H), 2.77 (s, 3H), 2.20 (s, 3H).

Reference： [1]Patent: US2010/29684,2010,A1 .Location in patent: Page/Page column 5; 15
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 7653 - 7668

40
[ 61995-20-8 ]
[ 1774-47-6 ]
[ 1047655-54-8 ]

Yield	Reaction Conditions	Operation in experiment
60%		To a solution of trimethylsulfoxonium iodide (3.1 g) in dimethyl sulfoxide (40 mL) was added sodium hydride (570 mg), and the mixture was stirred at room temperature for 1 hr. A solution of benzyl 3-oxopiperidine-1-carboxylate (3.0 g) in dimethyl sulfoxide (10 mL) was added under ice-cooling, and the mixture was stirred at room temperature for 16 hr. To the reaction solution was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (30% ethyl acetate/hexane to 50% ethyl acetate/hexane) to give the object product (1.9 g, 60%). 1H NMR (300 MHz, CDCl3) delta ppm 1.64-1.88 (m, 4H) 2.65-2.71 (m, 2H) 3.42-3.54 (m, 4H) 5.13 (s, 2H) 7.25-7.37 (m, 5H)

Reference： [1]Patent: US2010/69351,2010,A1 .Location in patent: Page/Page column 34-35

41
[ 1158098-73-7 ]
[ 1774-47-6 ]
[ 1211284-25-1 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 1116 - 1119

42
[ 77532-88-8 ]
[ 1774-47-6 ]
[ 1239331-76-0 ]

Reference： [1]Helvetica Chimica Acta,2010,vol. 93,p. 1048 - 1051

43
[ 1013112-48-5 ]
[ 1774-47-6 ]
[ 1239331-80-6 ]

Reference： [1]Helvetica Chimica Acta,2010,vol. 93,p. 1048 - 1051

44
[ 1774-47-6 ]
[ 123577-99-1 ]
[ 1239766-82-5 ]

Reference： [1]Organic Letters,2010,vol. 12,p. 3772 - 3775

45
[ 29943-42-8 ]
[ 1774-47-6 ]
[ 185-72-8 ]

Yield	Reaction Conditions	Operation in experiment
70%		NaH (0.88g, 23.26mmol, 60% dispersion in mineral oil) was added to a suspension of trimethylsulfonoxonium iodide (5.15g, 23.26mmol) in THF (40mL). The reaction mixture was heated at reflux for 3h, then tetrahydro-4H-pyran-4-one (1.82mL, 20.0mmol) was added, and the mixture was held at reflux for a further 2h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was redissolved in DCM (40mL) and any solid material removed by filtration. The filtrate was concentrated in vacuo to give 1,6-dioxaspiro[2,5]octane as a colorless oil (1.60g, 70%). Data are consistent with literature [28]. 1H NMR (400MHz, CDCl3): delta=3.89-3.76 (m, 4H), 2.68 (s, 2H), 1.90-1.81 (m, 2H), 1.56-1.48 (m, 2H). 13C NMR (100MHz, CDCl3): delta=66.7 (2C), 56.6, 54.0, 34.0 (2C).
63%		Trimethylsulfoxonium iodide (286 mg, 13 mmol) was dissolved in DMSO (20 mL) under an atmosphere of nitrogen. NaH (60% dispersion in mineral oil, 520 mg, 13 mmol) was then added portion-wise (NB. vigorous effervescence observed). The resultant suspension was stirred at rt for 1 h whereupon tetrahydro-4/-/-pyran-4-one 1-107 (0.93 mL, 10 mmol) was added dropwise. The reaction mixture was stirred at rt for an additional 1 h where it was then poured into a water / ice slurry. The aqueous phase was extracted with Et.20 (x 3) and the combined organic extracts washed with water and brine before drying over MgSC>4. Concentration in vacuo provided the title compound as a pale yellow oil (725 mg, 6.3 mmol, 63%).
43%		A suspension of trimethylsulfoxonium iodide (28.6 g, 130 mmol) in DMSO (200 mL) in two neck RBF (500 mL) at room temperature, NaH (5.19 g, 130 mmol, 60% in mineral oil) was added in portions under N2 pressure. Stirring was continued for one hour, then a solution of dihydro-2H-pyran-4(3H)-one (10 g, 100 mmol) in DMSO (10 mL) was added dropwise over 5 min. The reaction mixture was stirred at room temperature for 1 hr, then poured into ice-water (300 mL) and extracted with Et20 (2 x 200 mL). The organics were washed with water and brine, dried over MgSO4, filtered and concentrated to give 1,6-dioxospiro[2.5]octane (4.9 g, 42.9 mmol, 43.0% yield) as a colorless oil.

43.0%		Step 1: 1,6-Dioxaspiro[2.5]octane To a suspension of trimethylsulfoxonium iodide (28.6 g, 130 mmol) in DMSO (200 mL) in a two-neck RBF (500 mL) was added NaH (5.19 g, 130 mmol, 60% in mineral oil) in portions under N2 atomsphere at room temperature. Stirring was continued for one hour, then a solution of dihydro-2H-pyran-4(3H)-one (10 g, 100 mmol) in DMSO (10 mL) was added dropwise over 5 min. The reaction mixture was stirred for 1 hr at room temperature, then poured into ice-water (300 mL) and extracted with Et2O (2 x 200 mL). The organic was washed with water and brine, dried over MgSO4, filtered, and concentrated to give 1,6-dioxaspiro[2.5]octane (4.9 g, 42.9 mmol, 43.0 % yield) as colorless oil. 1H NMR (400 MHz , Chloroform-d) delta: 1.52 - 1.59 (m, 2 H) 1.89 (ddd, J=13.20, 8.40, 4.67 Hz, 2 H) 2.71 (s, 2 H) 3.79 - 3.95 (m, 4 H).
43%		Trimethylsulfonium iodide (28.6 g, 130 mmol) in DMSO (200 mL) for two-neck RBF (500 mL)NaH (5.19 g, 130 mmol, 60% in mineral oil) was added in portions to the suspension at room temperature under N2 pressure.Keep stirring for one hour,A solution of dihydro-2H-pyran-4(3H)-one (10 g, 100 mmol) in DMSO (10 mL) was then added dropwise over 5 min.The reaction mixture was stirred at room temperature for 1 hr.Then pour ice-water (300 mL) and use Et 2 O (2 x 200 mL)extraction. The organic liquid is washed with water and saline solution.Dry over MgSO 4 , filter, and concentrate.Get 1,6-dioxaspiro[2.5]octane(4.9 g, 42.9 mmol, 43.0% yield)Colorless oil.

Reference： [1]ChemMedChem,2010,vol. 5,p. 65 - 78
[2]Bioorganic Chemistry,2020,vol. 96
[3]Patent: WO2017/93543,2017,A2 .Location in patent: Page/Page column 114
[4]Patent: TWI609011,2017,B .Location in patent: Page/Page column 68; 69
[5]Patent: EP2680844,2016,B1 .Location in patent: Paragraph 0128
[6]Patent: TW2018/8946,2018,A .Location in patent: Page/Page column 59

46
[ 1774-47-6 ]
[ 70201-43-3 ]
[ 1255713-79-1 ]

Yield	Reaction Conditions	Operation in experiment
		Example 28: Synthesis of 2-chloro-4-{4-(oxetan-2-yl)pyridin-3-yl)benzonitrile 28a 28 Step 1·. 3-bromo-4-(oxetan-2-yl)pyridine (28a) A 500 mL round-bottomed flask was charged with trimethylsulfoxonium iodide (1 1.83 g, 53.8 mmol) in DMSO (80 ml), sodium hydride (1.989 g, 49.7 mmol) was added. After stirring for 15min, a solution of 3-biOmoisonicotinaldehyde (5g, 26.9 mmol) in DMSO (20 ml) was added slowly to the reaction. After 10min, The reaction mixture was diluted with water and EtOAc. The mixture was washed with H20 and brine. The organic was dried over Na2S04, filtered and concentrated to give crude intermediate 2.69g without further purification.A 100 mL round-bottomed flask was charged with trimetylsulfoxonium iodide (5.92 g, 26.9 mmol) in t-BuOH (20 ml). Potassium tert-butoxide (3.02 g, 26.9 mmol) was added. After stirring for 15min at 50C, a solution of the above intermediate (2.69g) in DMSO (20 ml) was added slowly to the reaction. After 16h, the reaction mixture was diluted with water and EtOAc. The mixture was extracted with ethyl acetate and washed with H20 and brine to give 462mg of crude title compound. ESI-MS mlz. 216.1 [M+1]+, Retention time 1.01 min;1HNMR (CDCI3, 400.342 MHz) delta ppm 2.50-2.59 (m, 1 H), 3.31-3.39 (m, 1 H), 4.65-4.70 (m, 1H), 4.87-4.92 (m, 1 H), 5.91 (t, J =8 Hz, 1H), 7.95 (d, J = 8 Hz, 1 H), 8.68 (d, J = 8 Hz, 1H), 8.73 (s, 1 H).

Reference： [1]Patent: WO2011/61168,2011,A1 .Location in patent: Page/Page column 72-73

47
[ 2058-72-2 ]
[ 1774-47-6 ]
[ 1330786-80-5 ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 9757 - 9764
[2]Green Chemistry,2011,vol. 13,p. 2553 - 2560
[3]European Journal of Medicinal Chemistry,2015,vol. 102,p. 413 - 424

48
[ 28957-72-4 ]
[ 1774-47-6 ]
[ 1222495-91-1 ]

Yield	Reaction Conditions	Operation in experiment
		7.1/ 8-Benzyl-spiro[8-azabicyclo[3.2.1]octane-3,2'-oxirane] Trimethyl sulfoxonium iodide (3.07 g, 13.9 mmol) is placed in 18 ml of DMSO under nitrogen in the presence of sodium hydride dispersed at 60% in oil (0.56 g, 13.9 mmol). After stirring for 30 min at ambient temperature, 8-benzyl-8-aza-bicyclo[3.2.1]octan-3-one (2.0 g, 9.3 mmol) solubilized in 3 ml of DMSO is slowly added. The reaction medium is kept stirring for 4 h and then kept without stirring for 60 h, After hydrolysis, and extraction with ethyl acetate, the organic phase is washed with a saturated aqueous sodium chloride solution and dried over MgSO4. 2.04 g of 8-benzyl-spiro[8-azabicyclo[3.2.1]octane-3,2'-oxirane], subsequently used as it is, are obtained. [M+H+]=230

Reference： [1]Patent: US2011/294809,2011,A1 .Location in patent: Page/Page column 12

49
[ 18362-30-6 ]
[ 1774-47-6 ]
C₈H₇ClO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2906 - 2911

50
[ 34333-12-5 ]
[ 1774-47-6 ]
C₉H₉ClO₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 2906 - 2911

51
[ 619-22-7 ]
[ 1774-47-6 ]
[ 140-29-4 ]
(1R,2R)-2-(3-(dimethylamino)phenyl)-1-phenylcyclopropanecarbonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 780 - 785

52
[ 51628-12-7 ]
[ 60656-87-3 ]
[ 1774-47-6 ]
(1R,2S)-2-(benzyloxymethyl)-1-(4-iodophenyl)cyclopropanecarbonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 780 - 785

53
[ 21531-47-5 ]
[ 1774-47-6 ]
[ 1416324-50-9 ]

Yield	Reaction Conditions	Operation in experiment
		Methyl 1-oxaspiror2.51octane-5-carboxylate To a solution of trimethylsulfoxonium iodide (53.3 g, 242 mmol) in dry DMSO (300 ml.) under N2, was added NaH (9.69 g, 242 mmol) portionwise over 30 min. This light yellow mixture was stirred at rt for 1 h The reaction mixture was cooled in an ice bath and treated with <strong>[21531-47-5]methyl 3-oxocyclohexanecarboxylate</strong> (29.0 g, 186 mmol) dropwise while maintaining a temperature at or below 27C. The resulting reaction mixture was allowed to warm slowly to rt and stir overnight. The reaction was diluted with water and extracted with DCM. The combined organics were washed with water, dried over MgS04, filtered, and concentrated to provide the crude title compound (31.8 g, 85 % crude yield) which was used without further purification. 1H NMR (400 MHz, CDCI3) delta 3.66 (s, 3H), 2.71 (m, 1 H), 2.65 (d, J = 1.76 Hz, 2H), 2.00 (dd J = 1 1.8, 13.6 Hz, 2H), 1.74 - 1.85 (m, 2H), 1.60 - 1.74 (m, 1 H), 1.40 - 1.56 (m, 2H), 1.17 - 1.32 (m, 1 H).
		[0107] To a solution of trimethylsulfoxonium iodide (53.3 g, 242 mmol) in dry DMSO (300 mL) under N2, was addedNaH (9.69 g, 242 mmol) portionwise over 30 min. This light yellow mixture was stirred at rt for 1 h The reaction mixturewas cooled in an ice bath and treated with <strong>[21531-47-5]methyl 3-oxocyclohexanecarboxylate</strong> (29.0 g, 186 mmol) dropwise whilemaintaining a temperature at or below 27 C. The resulting reaction mixture was allowed to warm slowly to rt and stirovernight. The reaction was diluted with water and extracted with DCM. The combined organics were washed with water,dried over MgSO4, filtered, and concentrated to provide the crude title compound (31.8 g, 85 % crude yield) which wasused without further purification. 1H NMR (400 MHz, CDCl3) delta 3.66 (s, 3H), 2.71 (m, 1 H), 2.65 (d, J = 1.76 Hz, 2H), 2.00(dd J = 11.8, 13.6 Hz, 2H), 1.74 - 1.85 (m, 2H), 1.60 - 1.74 (m, 1H), 1.40 - 1.56 (m, 2H), 1.17 - 1.32 (m, 1 H).

Reference： [1]Patent: WO2012/174342,2012,A1 .Location in patent: Page/Page column 65
[2]Patent: EP2720697,2016,B1 .Location in patent: Paragraph 0106; 0107

54
[ 1774-47-6 ]
[ 113400-36-5 ]
benzyl (2S)-2-((tert-butoxycarbonyl)amino)-6-(dimethyl(oxo)-λ⁶-sulfanylidene)-5-oxohexanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%		At room temperature, tertiary butyl alcohol potassium (11.8 g, 1.1 eq) added trimethyl [...] (26.0 g, 1 . 25 eq) tetrahydrofuran (100 ml) and DMSO (150 ml) solution, stirring at the room temperature 1 h after, lowering the temperature to -10 C. To the reaction is dropped in the N - Boc - L - pyroglutamic acid benzyl ester (compound SM, 30.2 g, 1.0 eq) tetrahydrofuran (60 ml) solution, after dropping in the -10 C to continue stirring. TLC detection after the reaction, the reaction temperature to room temperature slowly, by adding 20% aqueous ammonium chloride solution (82 ml) quenching the reaction, extracted with ethyl acetate three times, the combined organic phase is used in 10% NaCl aqueous solution washing, drying with anhydrous sodium sulfate, filtered, concentrated, gain the light yellow oil of 40 g, yield 100%.
96%	With potassium carbonate; In dimethyl sulfoxide; at 50℃; for 23h;	In a 3L three-necked flask, 900 mL of dimethyl sulfoxide and 55.2 g (2.0 eq, 250.9 mmol) of trimethylsulfoxonium iodide were added. 70.0 g (4.0 eq, 506.9 mmol) of potassium carbonate and 40.0 g (1.0 eq, 125.4 mmol) of N-Boc-pyroglutamic acid benzyl ester were heated to 50 C for 23 h. After that, the heating was stopped, and 500 mL of a saturated aqueous ammonium chloride solution was added dropwise. After the dropwise addition, 500 mL of purified water was added thereto, and the mixture was extracted with ethyl acetate (500 mL × 2). The organic phase was combined, washed with saturated brine and dried over anhydrous sodium sulfate. Concentrated under reduced pressure to give a pale yellow solid product 49.5 g, yield 96%, purity 96.0%,
		Example 1aBenzyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) may be prepared as described below.Dimethylsulfoxide (DMSO; 500 ml) was added to a mixture of trimethylsulfoxonium iodide (ME3SOI; 79.2 g, 360 mmol, 1.15 eq) and potassium tert-butoxide (KOtBu; 38.6 g, 344.4 mmol, 1.1 eq) in tetrahydrofuran (THF; 400 ml) at room temperature. The mixture was stirred until the reaction was deemed to be complete and cooled to -12 C. A solution of (S)-5-oxo-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester (100 g, 313.1 mmol, 1 eq) in tetrahydrofuran (THF; 300 ml) was added slowly. The mixture was stirred at -12 C. until the reaction was deemed to be complete. The reaction was quenched by the addition of saturated aqueous ammonium chloride (500 ml) and water (300 ml). The product was extracted with ethyl acetate (1000 ml), and the resulting organic solution was washed with aqueous sodium chloride. The organic layer was concentrated in vacuo to a final volume of 600 ml.To this solution was added O-benzylhydroxylamine hydrochloride (BnONH2HCl; 52.5 g, 328.8 mmol, 1.05 eq) and ethyl acetate (400 ml). The mixture was stirred at reflux until the reaction was deemed to be complete. The mixture was cooled and washed with water and saturated sodium chloride. The organic layer was concentrated in vacuo to afford a solution of (S)-5-Benzyloxyimino-2-tert-butoxycarbonylamino-6-chloro-hexanoic acid benzyl ester in ethyl acetate.Methane sulfonic acid (MSA; 61 ml, 939.3 mmol, 3 eq) was added to this solution. The solution was stirred at 42 C. until the reaction was deemed to be complete. The solution was added to a solution of potassium bicarbonate (156.7 g, 1565.5 mmol, 5 eq) in water (500 ml) and the resulting mixture was stirred vigorously at 52 C. until the reaction was deemed to be complete. The organic layer was washed with aqueous sodium chloride and concentrated in vacuo to afford a solution of (S)-5-Benzyloxyimino-piperidine-2-carboxylic acid benzyl ester in ethyl acetate.Propanoic acid (140.6 ml, 1878.6 mmol, 6 eq) was added to a suspension of sodium borohydride (23.2 g, 626.2 mmol, 2 eq) in ethyl acetate (600 ml) and held until the reaction was deemed to be complete. The resulting solution was added to a solution of benzyl (2S)-5-[(benzyloxy)imino]piperidine-2-carboxylic acid benzyl ester in ethyl acetate (600 ml total volume) and sulphuric acid (83.4 ml, 1565 mmol, 5 eq) at -20 C. and held until reaction was deemed to be complete. The reaction was quenched by the addition of water (1000 ml), then neutralized with aqueous ammonia solution. The organic layer was washed with water and concentrated in vacuo to 400 ml. The solution was warmed to 45 C. and held at this temperature. Methanol (200 ml) at 40 C. was added, followed by a freshly prepared solution of oxalic acid dihydrate (39.5 g, 313.1 mmol) in methanol (100 ml). The mixture was cooled and the product was isolated by filtration. The solid was washed with an ethyl acetate/methanol mixture, then with ethyl acetate. The solid was dried to give benzyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate ethanedioate (1:1) as a single isomer (79.4 g, 185 mmol, 59%).

Trimethylsulfonyl iodide (16 g, 72.7 mmol) and potassium tert-butoxide (8 g, 71.3 mmol) were added to tetrahydrofuran (100 mL), DMSO (100 mL) was added, stirred and reacted at 25C for 2 h, cooled to about -10C. The solution of <strong>[113400-36-5](S)-2-benzyl 1-tert-butyl 5-oxopyrrolidine-1,2-dicarboxylate</strong> (20 g, 62.6 mmol) in tetrahydrofuran (60 mL) was added. After addition, the reaction was performed at a low temperature under stirring for 8 h. The reaction solution was quenched with an aqueous saturated solution (100 mL) of ammonium chloride, ethyl acetate (100 mL*3) was added for extraction, and the organic phases were combined, dried over anhydrous sodium sulfate, filtrated, concentrated to 120 mL. The crude product was directly used in the next reaction step.

Reference： [1]Patent: CN109912499,2019,A .Location in patent: Paragraph 0054-0056
[2]Patent: CN108822014,2018,A .Location in patent: Paragraph 0035-0037; 0041; 0043; 0051-0052
[3]Patent: US2012/323010,2012,A1 .Location in patent: Page/Page column 14-15
[4]Organic Process Research and Development,2016,vol. 20,p. 1799 - 1805
[5]Patent: EP3281942,2018,A1 .Location in patent: Paragraph 0173; 0174

55
[ 37722-82-0 ]
[ 1774-47-6 ]
methyl 1-oxaspiro[2.5]octane-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 27℃;Inert atmosphere; Cooling with ice;	Methyl 1-oxaspiror2.5loctane-5-carboxylateTo a solution of trimethylsulfoxonium iodide (53.3 g, 242 mmol) in dry DMSO (300 ml.) under N2, was added sodium hydride (9.69 g, 242 mmol) portionwise over 30 min. This light yellow mixture was stirred at RT for 1 h. The reaction mixture was then cooled in an ice bath and treated with methyl 3-oxocyclohexanecarboxylate (29.0 g, 186 mmol) dropwise while maintaining a temperature at or below 27 C. The resulting reaction mixture was allowed to warm slowly to RT and stir overnight. The reaction was diluted with water and extracted with DCM. The combined organics were washed with water, dried over MgS04, filtered, and concentrated to provide methyl 1-oxaspiro[2.5]octane-5-carboxylate (31.8 g, 85 % yield) which was used without further purification. H NMR (400 MHz, CDCI3) delta 3.66 (s, 3H), 2.71 (m, 1 H), 2.65 (d, J = 1.76 Hz, 2H), 2.00 (dd J = 1 1.8, 13.6 Hz, 2H), 1.74 - 1.85 (m, 2H), 1.60 - 1.74 (m, 1 H), 1.40 - 1.56 (m, 2H), 1.17 - 1.32 (m, 1 H).

Reference： [1]Patent: WO2013/12500,2013,A1 .Location in patent: Page/Page column 63

56
[ 1774-47-6 ]
[ 130753-13-8 ]
[ 1073923-19-9 ]

Yield	Reaction Conditions	Operation in experiment
		Example 84A benzyl 8-azaspiro[bicyclo[3.2.1]octane-3,2'-oxirane]-8-carboxylate To a 500-mL, three-necked, round-bottomed flask equipped with a magnetic stirring bar, a thermometer, and a condenser was charged tetrahydrofuran (163 mL), potassium tert-butoxide (6.6 g, 95% pure) and trimethylsulfoxonium iodide (13.0 g). The mixture was heated to reflux and stirred for 3 hours. A solution of <strong>[130753-13-8]benzyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate</strong> (10.0 g) in tetrahydrofuran (37 mL) was added in one portion. The reaction mixture was refluxed for another 2 hours. The mixture was cooled to room temperature and diluted with toluene (100 mL) and water. The water layer was separated and extracted with toluene (250 mL). The combined organic layers were washed with water (340 mL) and concentrated under vacuum to provide the title compound.

Reference： [1]Patent: US2013/96120,2013,A1 .Location in patent: Paragraph 1192

57
[ 24393-52-0 ]
[ 1774-47-6 ]
[ 4157-47-5 ]

Reference： [1]Organic Letters,2013,vol. 15,p. 1350 - 1353

58
[ 5048-82-8 ]
[ 1774-47-6 ]
[ 853404-00-9 ]
[ 853403-99-3 ]

Yield	Reaction Conditions	Operation in experiment
70 mg		To a suspension of sodium hydride (36 mg, 0.89 mmol) in DMSO (2mL) was added the solid trimethyl sulfoxonium iodide (185 mg, 1.05 mmol). The mixture was stirred for 25min before a solution of <strong>[5048-82-8]ethyl (E)-3-(4-aminophenyl)prop-2-enoate</strong> (100 mg, 0.52 mmol) in DMSO (2mL) was added quickly at RT. The mixture was left to stir overnight. The bulk mixture was quenched with NH4CI (sat.) and the mixture diluted with water and EtOAc. The layers were separated and the aqueous layer extracted into EtOAc (3x30mL). The organic fractions were combined, dried with brine then MgS04 and the solvent removed. Flash chromatography on silica gel, eluting with 20-50percent ethyl acetate gradient in n-heptane, gave ethyl (lR,2R)-2-(4aminophenyl) cyclopropanecarboxylate, 70mg. *H NMR (400 MHz, CDC13) delta 6.96 - 6.89 (m, 2H), 6.68 - 6.61 (m, 2H), 4.17 (q, J = 7.1 Hz, 2H), 2.44 (ddd, J = 9.2, 6.6, 4.2 Hz, 1H), 1.80 (ddd, J = 8.4, 5.2, 4.2 Hz, 1H), 1.53 (ddd, J = 9.2, 5.2, 4.5 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H), 1.24 (ddd, J = 8.3, 6.6, 4.5 Hz, 1H).

Reference： [1]Patent: WO2013/91011,2013,A1 .Location in patent: Page/Page column 60

59
[ 1774-47-6 ]
[ 135716-08-4 ]
[ 1242268-17-2 ]

Yield	Reaction Conditions	Operation in experiment
79%		To a solution of trimethylsulfoxonium iodide (140 g, 636 mmol) in dimethyl sulfoxide (800 mL) was added potassium tert-butoxide (71.2 g, 634 mmol) in one portion at 20 C. After the reaction mixture had been stirred at 20 C. for 1.5 hours, a solution of C31 (95.0 g, 353 mmol) in dimethyl sulfoxide (800 mL) was added drop-wise, and stirring was continued at 20 C. for 16 hours. Saturated aqueous sodium chloride solution (2.0 L) was then added; the resulting mixture was neutralized by addition of ammonium chloride, and extracted with ethyl acetate (3.0 L). The combined organic layers were washed sequentially with water (2×1.0 L) and with saturated aqueous sodium chloride solution (2.0 L), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluent: 10:1 petroleum ether/ethyl acetate) afforded C32 as a yellow oil. 1H NMR analysis indicated that extraneous aliphatic material was present. Yield: 80 g, 280 mmol, 79%. 1H NMR (400 MHz, chloroform-d), C32 peaks only: delta 4.19-4.09 (m, 2H), 3.55-3.39 (m, 3H), 3.27 (ddd, J=13.0, 7.0, 4.5 Hz, 1H), 1.76-1.64 (m, 2H), 1.56 (dd, J=8.0, 5.5 Hz, 1H, assumed; partially obscured by water peak), 1.47 (s, 9H), 1.47-1.37 (m, 2H), 1.27 (t, J=7.0 Hz, 3H), 1.17 (dd, J=5.0, 5.0 Hz, 1H), 0.93 (dd, J=8.0, 4.5 Hz, 1H).
79%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃; for 17.5h;	To a solution of trimethylsulfoxonium iodide (140 g, 636 mmol) in dimethyl sulfoxide (800 ml_) was added potassium fe/f-butoxide (71 .2 g, 634 mmol) in one portion at 20 C. After the reaction mixture had been stirred at 20 C for 1 .5 hours, a solution of C15 (95.0 g, 353 mmol) in dimethyl sulfoxide (800 ml_) was added drop-wise, and stirring was continued at 20 C for 16 hours. Saturated aqueous sodium chloride solution (2.0 L) was then added; the resulting mixture was neutralized by addition of ammonium chloride, and extracted with EtOAc (3.0 L). The combined organic layers were washed sequentially with water (2 x 1 .0 L) and with saturated aqueous sodium chloride solution (2.0 L), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Eluent: 10:1 petroleum ether / EtOAc) afforded C16 as a yellow oil. 1H NMR analysis indicated that extraneous aliphatic material was present. Yield: 80 g, 280 mmol, 79%. NMR (400 MHz, Chloroform-d): d 4.19 - 4.09 (m, 2H), 3.55 - 3.39 (m, 3H), 3.27 (ddd, 1 H), 1 .76 - 1 .64 (m, 2H), 1 .56 (dd, 1 H, assumed; partially obscured by water peak), 1 .47 (s, 9H), 1 .47 - 1 .37 (m, 2H), 1 .27 (t, 3H), 1 .17 (dd, 1 H), 0.93 (dd, 1 H).
54%		Step 2: Sodium hydride (60% in mineral oil) (2.06 g, 85.8 mmol) was added to dimethylsulfoxide (100 mL) at 15C, and the mixture was stirred at 15C for 20 min. See Figure 6. Trimethylsulfoxonium iodide (19.0 g, 85.8 mmol) was added, and the reaction mixture was stirred for 2h, then 165b (7.72 g, 28.7 mmol) was added and the resulting mixture was stirred at 15 C for 50h. Water (100 mL) was added, and the mixture was extracted with EtOAc (200 mL x 3). The combined organic extracts were washed with brine (100 mL x 2), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column (petroleum ether: EtOAc = 2 : 1) to yield 6-ieri-butyl 1-ethyl 6- azaspiro[2.5]octane-l,6-dicarboxylate 165c (4.4 g, 54%) as a colorless oil. *H NMR (400 MHz, CD3CN): delta 4.06 - 4.04 (m, 2H), 3.40 - 3.18 (m, 4H), 1.92 - 1.90 (m, 1H), 1.59 - 1.50 (m, 3H), 1.39 - 1.30 (m, 10H), 1.19 - 1.16 (m, 3H), 1.03 - 1.01 (m, 1H), 0.91 - 0.93 (m, 1H).

147 g

Step 2. 6-tert-Butyl 1 -ethyl 6-a2aspiro[2.51octane- 1 .6-dicarboxylate. A solution of trimethylsulfoxonium iodide (61 8 g, 2.81 mol, 3.00 equiv) and t-BuO (3 1 5 g, 2.81 mol, 3.00 equiv) in DMSO (5 L) was stirred at rt for 1 h. tert-Butyl 4-(2- ethoxy-2-oxoethylidene)piperidine- l -carboxylate (252 g, 935.63 mrnol, 1 .00 equiv ) was then added in several portions. The reaction mixture was stirred at rt overnight and then quenched by the addition of 1 0 L of saturated NH4CI solution. The resulting mixture was extracted with 3x3 L of ethyl acetate. The organic combined layers were washed with 2x 1 .5 L of brine The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a sil ica gel column eluted with ethyl acetate/petroleum ether ( 1 /1 0) to give 147 g of 6-tert-buty 1 1 -ethyl 6-azaspiro[2.5]octane- l ,6-dicarboxylate as yellow oil. TLC: ethyl acetate/petroleum ether = 1 :2, | = 0.5.

Reference： [1]Patent: US2019/382384,2019,A1 .Location in patent: Paragraph 0473; 0475
[2]Patent: WO2019/239371,2019,A1 .Location in patent: Page/Page column 57
[3]Patent: WO2015/949,2015,A1 .Location in patent: Page/Page column 117
[4]Patent: WO2013/127269,2013,A1 .Location in patent: Page/Page column 189

60
[ 1774-47-6 ]
[ 101385-93-7 ]
[ 301226-25-5 ]

Yield	Reaction Conditions	Operation in experiment
18.6%		[00524] To a mixture of t-BuOK (727.1 mg, 6.5 mmol, 1.20 eq) in DMSO (10 mL), was added trimethylsulfoxonium iodine (1.4 g, 6.5 mmol, 1.20 eq) by portions. The mixture was stirred at 15 C for 0.5 h. DME (5 mL) was added, and the mixture was cooled to 0 C. A solution of 144-1 (1.0 g, 5.4 mmol, 1.00 eq) in DMSO (2 mL) and DME (4 mL) was added dropwise at 0 C. The resulting mixture was stirred at 0 C for 2 h. TLC showed the reaction was complete. The mixture was diluted with water (20 mL), and extracted with DCM (20 mL*3). The combined organic layers were dried over anhydrous Na2S04, and concentrated under vacuum. The residue was purified by silica gel chromatography to provide 144-2 (200.0 mg, 1.0 mmol, 18.6% yield). 1HNMR (400MHz, CHLOROF ORM-
		Step 1) 5-(tert-butoxycarboxyl)-l-oxa-5-azaspiro\|"2.4"\|heptane [0209] To themixture of trimethylsulfoxonium iodide (2.57 g, 11.7 mmol) in DMSO (8.8 mL) was added NaH (351 mg, 80% dispersion in mineral oil) at 10C. The mixture was stirred at rt for 2 h, then a solution of l-(tert-butoxymethyl)pyrrolidin-3-one (2.00 g, 10.8 mmol) in DMSO (3.0 mL) was added. The reaction was continued to stir for 3 h, then quenched with ice water (50 mL)followed by brine (50 mL), and then extracted with DCM (100 mL x 3). The combined organic phases were washed with brine (50 mL), dried over anhydrous Na2S04, and concentrated in vacuo to yield viscous brown oil, which was used for the next step without further purification.

Reference： [1]Patent: WO2018/204532,2018,A1 .Location in patent: Paragraph 00524; 00564
[2]Patent: WO2013/138210,2013,A1 .Location in patent: Paragraph 0209

61
[ 23499-01-6 ]
[ 1774-47-6 ]
[ 1527518-96-2 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of trimethylsulfoxonium iodide (1 1.50 g, 52 mmol) in t-BuOH (100 mL) was added t-BuOK (5.00 g , 52 mmol) and the reaction stirred at 50C for 1 .5 h. 2-3 (4.60 g, 21 mmol) was added and the reaction mixture was stirred at 50C for a further 48h. The mixture was poured into H20 (300 mL) and extracted with EtOAc (200 mL x 3). The organic layers were combined and washed with brine (200 mL), dried (MgS04), filtered and concentrated. The residue obtained was washed with EtOAc (20 mL) and the yellow solid obtained dried under reduced pressure to afford the product (2.30 g, 44%). The structure was confirmed by LC-MS spectra. It was used for the next step without further purification. TLC:Rf=0.20 (silica gel,EtOAc/Pet ether=1/1 , v/v)LC-MS :[M+1]+=249

Reference： [1]Patent: WO2014/32,2014,A1 .Location in patent: Page/Page column 37; 38

62
[ 1774-47-6 ]
[ 105258-93-3 ]
[ 1527518-91-7 ]

Yield	Reaction Conditions	Operation in experiment
11%		To a stirred solution of trimethylsulfoxonium iodide (4.20 g, 20.5 mmol) in t-BuOH (100ml_) was added KOtBu (1 1 .00 g 50.0 mmol) and the reaction heated at 50C for 1 h. 1-2 (4.80 g, 42.8 mmol) was added and the resulting mixture was stirred at 50 C for a further 48h, then quenched by addition of saturated NH4CI and EA. The aqueous layer was extracted twice with EA and the combined organic layers were then washed with brine, dried (Na2S04) and concentrated. The crude product was purified by flash chromatography (EA/PE.1 :2) to obtain compound D (530 mg , 1 1 %) as yellow oil. TLC:Rf=0.36 (silica gel,EA:PE=1 :2, v/v) LC-MS :[M+1]+= 234; [M+Na]=256 1 H-NMR (400MHz,CDCI3)5(ppm): 7.36 - 7.32 (m, 5H), 5.08(s,2H), 4.51 (t, J=7.5 Hz, 2H), 4.23-4.14 (m, 4H), 2.83 (t, J=7.5 Hz, 2 H).

Reference： [1]Patent: WO2014/32,2014,A1 .Location in patent: Page/Page column 34

63
[ 61995-20-8 ]
[ 1774-47-6 ]
[ 1527519-12-5 ]

Yield	Reaction Conditions	Operation in experiment
11%		To a suspension of trimethylsulfoxonium iodide (35.20 g, 0.16 mol) in t-BuOH (150 mL) was added t-BuOK (17.95 g, 0.16 mol) at 50C , the mixture turned to a cloudy suspension. The mixture was stirred at the same temperature for 1.5h. Compound 5-C (14.90 g, 64 mmol) was then added at that temperature and the mixture stirred at 50C for another 48h. The reaction mixture was cooled to room temperature and partitioned between saturated aqueous NH4CI and EtOAc. The organic phase was separated, dried (MgS04), filtered and concentrated under reduce pressure. The residue obtained was purified silica gel columnchromatography (EtOAc/Pet ether=1/6) to give (2.0 g, 1 1 %) as colorless oil. The structure was confirmed by LC-MS and H-NMR spectra. TLC: Rf=0.52 silica gel EtOAc/Pet ether=1/1 LC-MS : 262 ([M+1]+), H-NMR: 7.33 (m, 5H), 5.14 (s, 2H), 4.66 - 4.43 (m, 2H), 3.82 (d, J = 13.0 Hz, 1 H), 3.67 - 3.07 (m, 3H), 2.37 (m, 2H), 1.99 - 1.35 (m, 4H).

Reference： [1]Patent: WO2014/32,2014,A1 .Location in patent: Page/Page column 45; 46

64
[ 1774-47-6 ]
[ 130312-02-6 ]
[ 1527519-33-0 ]

Yield	Reaction Conditions	Operation in experiment
18%		To a stirred solution of trimethylsulfoxonium iodide (32.70 g, 0.15 mol) in (100 mL) was added t-BuOK (14.30 g 0.13) and the reaction stirred at 50 C for 1 h. Intermediate C (13.00 g 60 mmol) was then added and the resulting mixture was stirred at 50C for a further 48 h. The reaction mixture was quenched by addition of saturated NH4CI solution and partitioned against EtOAc. The aqueous layer was extracted twice with EtOAc and the combined organic layers were then washed with brine, dried (Na2S04), filtered and concentrated. The crude product was purified by flash chromatography (EtOAc /Pet ether=1 :2) to give D (2.70 g 18%) as yellow oil. The structure was confirmed by LC-MS and H-NMR spectra. TLC:Rf=0.36(silica gel,EA:PE=1 :2, v/v) LC-MS : [M+H]+=248 ; [M+Na]=270.
12%		To a solution of trimethylsulfoxonium iodide in tert-butanol (78 mL) was added potassium tert-butanolate (11.6 g, 103.4 mmol). The mixture was stirred at 50 C for 1 hour and then <strong>[130312-02-6]benzyl 3-oxopyrrolidinyl-1-carboxylate</strong> (10.3 g, 47 mmol) was added. The mixture was stirred at 50 C for an additional 48 hours. The reaction was quenched with saturated ammonium chloride solution (200 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic layers were washed with saturated sodium chloride solution (100 mL), dried, and concentrated. The remaining residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 3:1) to give benzyl 1-oxa-6- azaspiro[3.4]octane-6-carboxylate (1.5 g, 12%) as a light yellow oil. LCMS m/z = 248.0 [M+H]+.

Reference： [1]Patent: WO2014/32,2014,A1 .Location in patent: Page/Page column 52
[2]Patent: WO2017/216726,2017,A1 .Location in patent: Page/Page column 582

65
[ 181269-69-2 ]
[ 1774-47-6 ]
[ 862669-17-8 ]

Yield	Reaction Conditions	Operation in experiment
75%		In a round-bottom flask, trimethylsulfoxonium iodide (3.10 g, 14.07 mmol) was dissolved in dimethyl sulfoxide (20 mL) and cooled to 0 C. Sodium hydride (0.675 g, 16.88 mmol; 60% dispersion in mineral oil) was added to the frozen mixture and the mixture was allowed to warm to room temperature and stirred for 2 h. This mixture was then re-cooled to 0 C and 1,1 -dimethylethyl 3-methyl-4-oxo-l-piperidinecarboxylate (3.0 g, 14.07 mmol) in dimethyl sulfoxide (2 ml) was added to the frozen mixture and then allowed to warm to room temperature. The reaction mixture was stirred for 2 h. Water was slowly added to the reaction mixture, which was then transferred to a separatory funnel containing dichloromethane. The layers were separated. The aqueous phase was extracted with dichloromethane (3x), and the combined organics were washed with brine (2x), dried over Na2S04, filtered, and concentrated to a yellow oil. Purification by silica gel chromatography (10-80% ethyl acetate/hexanes) afforded the title compound (2.4 g, 75%>) as a yellow oil. MS(ES)+ m/e 228.1 [M+H]+.

Reference： [1]Patent: WO2014/8223,2014,A2 .Location in patent: Page/Page column 137

66
[ 19099-93-5 ]
[ 1774-47-6 ]
[ 77211-75-7 ]

Yield	Reaction Conditions	Operation in experiment
80%		the sodium hydroxide (60%, 4.37 g, 109.25 mmol, 1.5 eq) was added to a solution oftrimethylsulfoxonium iodide (24.06 g, 109.32 mmol, 1.5 eq) in dry DMSO (0.10 L) at 0 C, and thenstirred at 0 C for 40 min. Benzyl 4-oxopiperidine-1-carboxylate (17.00 g, 72.88 mmol, 1 eq) [28] wasadded to the mixture and stirred for 2 h at 55 C. The reaction mixture was extracted with EtOAc(0.18 L) and brine (0.06 L). The organic layer was dried (Na2SO4) and concentrated in vacuo. Crudewas purified by flash column chromatography (hexanes/EtOAc) on silica gel column to give compound6 (14.50 g, 80%) as a yield oil. 1H-NMR (400 MHz, CDCl3)deltadeltadelta 7.42-7.28 (m, 5H), 5.15 (s, 2H), 3.82 (s, 2H),3.48 (t, J = 10.8 Hz, 2H), 2.70 (s, 2H), 1.83 (s, 2H), 1.45 (d, J = 10.4 Hz, 2H). ESI-MS (m/z): 247.9 [M + H]+.
76%		To a suspension of trimethylsulfoxonium iodide (1 1.7 g, 53.0 mmol) in DME (50 mL) under N2 was added KOf-Bu (6.49 g, 57.8 mmol). After 30 min this suspension was cooled to 0 C and a solution of benzyl 4-oxopiperidine-1-carboxylate (11.2 g, 48.2 mmol) in DME (20 mL) was added dropwise over 45 min. The reaction was allowed to warm to RT over 16 h before being quenched by the addition of water (150 mL). The mixture was then extracted with Et20 (3 x 100 mL), the combined organic phases were washed with brine (100 mL), dried over MgS04 and the volatiles removed in vacuo. To the resulting oil was added toluene (50 mL) and the volatiles removed in vacuo to give benzyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (9.00 g, 76%) as a yellow oil. 1H NMR (300 MHz, CDCI3): delta 7.41-7.28 (m, 5H), 5.16 (s, 2H), 3.93-3.75 (m, 2H), 3.55-3.39 (m, 2H), 2.71 (s, 2H), 1.93-1.73 (m, 2H), 1.53-1.37 (m, 2H).
69%		At 0 C., sodium hydride (600 mg, 60% in oil mineral, 15 mmol) was added to a solution of trimethylsulfoxonium iodide (3.3 g, 15 mmol) in DMSO (50 mL). The mixture was stirred for 40 min at RT, and then 4-oxo-piperidine-1-carboxylic acid benzyl ester (2.33 g, 10 mmol) was added. The mixture was stirred at 55 C. for 2 h, cooled to RT and poured into ice water. The crude mixture was extracted with EtOAc (2×50 mL) and the combined organic layers dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with EtOAc/PE (1:1) to afford 1-oxa-6-aza-spiro[2.5]octane-6-carboxylic acid benzyl ester as a colorless oil (1.7 g, 69%). LCMS (ESI): m/z=248.0 [M+1]+.

900 mg		To a mixture of iodo-trimethyl-oxo-sulfane (1.24 9,5.65 mmol) in DMSO (10 mL) was added NaH (617 mg, 15.43 mmol) at 20"C. The mixture was stirred at 20"C for 10 min. Benzyl 4-oxopiperidine-l-carboxylate (500 mg, 2.14 mmol) was added to the mixture. The mixture was stirred at 20"C for 3h. LCMS showed the reaction was completed. The mixture was poured into water (20 mL) and extracted with EtOAc (30 mL3). The combined organic layer was dried over Na2SOa, filtered, and concentrated under vacuum to afford crude benzyl l-oxa-6- azaspir o12.5 I octane-6-carboxyl ate (900 mg). LCM S ml z 248 . [M+H]
7.58 g	With potassium tert-butylate; In 1,2-dimethoxyethane; at 100℃; for 5h;	To a mixture of benzyl 4-oxopiperidine-1-carboxylate (11.7 g, 50 mmol) and trimethylsulfoxonium iodide (12.1 g, 55 mmol) in DME (200 mL) was added potassium tert-butoxide (6.17 g, 55 mmol), and stirred at 100 C for 5 h. Water was added at RT and the mixture was extracted with EtOAc. The organic layer was washed with water and brine, and dried over anhydrous Na 2SO 4, filtered, and concentrated in vacuo, The residue was purified by column chromatography on silica gel (gradient elution, EtOAc : hexane = 1 : 5 to 1 : 2) to give the title compound (7.58 g). MS: [M+H] + = 248.

Reference： [1]Molecules,2019,vol. 24
[2]Patent: WO2018/73602,2018,A1 .Location in patent: Page/Page column 60
[3]Patent: US2015/31674,2015,A1 .Location in patent: Paragraph 0301; 0302
[4]Chemical Communications,2015,vol. 51,p. 2388 - 2391
[5]Chemical Communications,2016,vol. 52,p. 4891 - 4893
[6]Patent: WO2016/123387,2016,A1 .Location in patent: Page/Page column 97
[7]Patent: WO2020/22323,2020,A1 .Location in patent: Paragraph 0425-0427

67
N-(4-fluorobenzyl)-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido)propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxamide [ No CAS ]
[ 1774-47-6 ]
[ 518048-05-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	With magnesium hydroxide; In water; at 100℃; for 7h;	Example 5 Preparation of Raltegravir (I) N-(4-fluorobenzyl)-2-(2-(5-methyl-1,3,4-oxadiazole-2-carboxamido) propan-2-yl)-1,6-dihydro-5-hydroxy-6-oxopyrimidine-4-carboxamide (VI) (50 gms), magnesium hydroxide (13.9 gms) trimethylsulfoxonium iodide (52.4 gms) and water (1.3 ml) were heated to 100 C. for 7 hour. The reaction was cooled to 20 C. and stirred for 15 minutes. An aqueous solution of sodium bisulfate (2M; 5 ml) was added and stirred for 30 to 45 minutes at 25 to 35 C., reaction mass was extracted with dichloromethane (400 ml) and solvent concentrated under reduced pressure. The product was isolated by crystallization from mixture of methanol-water (1:1). The resultant slurry was filtered and washed with mixture of methanol-water (50 ml) and dried to give Raltegravir (I). Yield: 46 gms Yield: 94%.

Reference： [1]Patent: US2015/45554,2015,A1 .Location in patent: Paragraph 0090-0092

68
[ 34846-90-7 ]
[ 1774-47-6 ]
[ 59425-00-2 ]

Yield	Reaction Conditions	Operation in experiment
50%		General procedure: Sodium hydride (60percent), (1.88 g, 0.047 mol), washed twice withhexane to remove the paraffin oil, was added to a clean well driedRB flask. Traces of solvent were removed by applying nitrogenusing evacuated carousel or ampoules. To the dried sodiumhydride, dry DMF (30 mL) was added under nitrogen atmosphere,followed by trimethylsulfoxonium iodide (10.35 g, 0.047 mol) insingle lot and the contents were stirred for 60 min at 40?45 C.This solution was added to a mixture of the compound 3a (10 g,0.046 mol) in DMF (5 mL) at 0 C under nitrogen atmosphere overa period of 15 min. The completion of reaction was checked by TLC.Then the reaction mixture was maintained for a period of 1?2 h atroom temperature and quenched by adding the reaction mixtureinto a solution of aqueous hydroiodic acid (10percent) solution at 0 C.The aqueous mixture was extracted with chloroform and theorganic layer was washed with 10percent sodium thiosulfate solutionto remove the excess iodine. The organic layer was concentratedand purified using column chromatography on silica gel (hexane/EtOAc) to afford the iodo compound 5a, as pale yellow colouroily liquid.

Reference： [1]Tetrahedron Letters,2015,vol. 56,p. 4031 - 4035

69
[ 775-16-6 ]
[ 1774-47-6 ]
[ 97266-84-7 ]

Yield	Reaction Conditions	Operation in experiment
97%		To an ice-cooled mixture of NaH (60%, 0.59 g, 14.83 mmol) and trimethylsulfoxonium iodide (2.76 g, 12.55 mmol) DMSO (10 mL) was added keeping the mixture at 10 C. After stirring for 10 mm at 10 C, the mixture was allowed to reach RT and left stirring at that temperature for 1 h. A solution of 1-benzylpyrrolidin-3-one (2 g, 11.41 mmol) in DMSO (10 mL) was added via syringe over 10 mm. The resulting reaction mixture was stirred for 1.5 h at RT, diluted with Et20 and quenched by the addition of saturated aqueous NH4CI. Phases were separated and aqueous one was backextracted with Et20. Combined organics were dried, filtered and concentrated under reduced pressure to give 5-benzyl-1- oxa-5-azaspiro[2.4]heptanes (p134, 2.10 g, y= 97%) that was used as such.MS (ES) (m/z): 190.1 [M÷H]
79%		To an ice-cooled mixture of NaH 60% dispersion in mineral oil (0.297 g, 7.42 mmol.) and trimethylsulfoxonium iodide (1.38 g, 6.28 mmol) was added DMSO (5 mL) keeping the mixture at 10 C. After stirred for 10 min at 10 C, it was allowed to reach T and left stirring at that temperature for 1 h. A solution of l-benzylpyrrolidin-3-one (0.92 m L, 5.71 mmol.) in DMSO (5 m L) was added via syringe. The mixture was stirred for 3 hrs at RT, diluted with Et20 and quenched by the addition of saturated aqueous N H4CI. Phases were separated and aqueous one was backextracted with Et20. Combined organics were dried, filtered and concentrated under reduced pressure. Crude 5-benzyl-l-oxa-5- azaspiro[2.4]heptane (P43, 850 mg, y= 79%) was used as such in next step. MS (ES) (m/z): 427.2 [M+H]+.
37.04%		To a stirred solution of trimethylsulfoxonium iodide (2.5 g, 11.4 mmol) in DMSO (20 mL) was added NaH (328.7 mg, 13.7 mmol) at 0C. The resulting mixture was stirred at 0C for 1 h before 1-benzyl-3-pyrrolidinone (2.0 g, 11.4 mmol) was added. The resulting mixture was stirred at 20C for additional 15 h until TLC (petroleum ether: EtOAc= 3:1) showed the reaction was completed. Water (50 mL) was added and the resulting mixture was extracted with EtOAc (20 mL) three times. The combined organic layer was washed with brined, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product, which was purified by silica gel flash chromatography (petroleum ether: EtOAc= from 5:1 to 3:1) to give 5-benzyl-1-oxa-5- azaspiro[2.4]heptane (800 mg, 37.04% yield) as yellow oil.< SUP>1< /SUP>H NMR (400MHz, (1271) CHLOROFORM-d) delta 7.40 - 7.31 (m, 4H), 7.30 - 7.24 (m, 1H), 4.14 (q, J=7.2 Hz, 1H), 3.72 - 3.60 (m, 2H), 2.89 - 2.85 (m, 2H), 2.85 - 2.77 (m, 2H), 2.77 - 2.68 (m, 1H), 2.61 (d, J=10.7 Hz, 1H), 2.22 (td, J=7.2, 14.1 Hz, 1H), 2.00 - 1.88 (m, 1H).

Preparation 59: 5-benzyl-1-oxa-5-azaspiro[2,4]heptanes (P59)To an ice- cooled mixture of NaH (60%, 0.59 g. 14.83 rnrnol) and Trimethylsulfoxonium iodide (2.76 g, 12.55 mrnoj) was added DMSO (10 mL) keeping the mixture at 10 C. After stirring for 10 min at 10 C, the mixture was allowed to reach RT and left stirring at that temperature for 1 h. A solution of 1- benzylpyrrolidin-3-one (2 g, 11.41 mmol) in DMSO (10 m L) was added via syringe over 10 min. The resulting reaction mixture was stirred for 1.5 h at RT, diluted with EtjO and quenched by the addition of saturated aqueous H4CL Phases were separated and aqueous one was backextracted with Et20. Combined organics were dried, filtered and concentrated under reduced pressure to give 5-benzyi-l- oxa-5-azaspiro[2.4]heptanes (p59. 2,10 g, crude material) that was used as such.MS (ES) (m/z): 190.1 [M+H]+.

Reference： [1]Patent: WO2016/42452,2016,A1 .Location in patent: Page/Page column 186
[2]Patent: WO2016/42453,2016,A1 .Location in patent: Page/Page column 91
[3]Patent: WO2018/178041,2018,A1 .Location in patent: Page/Page column 120
[4]Patent: WO2016/42451,2016,A1 .Location in patent: Page/Page column 97
[5]Synthesis,2018,vol. 50,p. 3696 - 3707
[6]Journal of Medicinal Chemistry,2020,vol. 63,p. 2434 - 2454

70
[ 6552-63-2 ]
[ 1774-47-6 ]
(4-chlorophenyl)-2-(4-methoxyphenyl)cyclopropylmethanone [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2016,vol. 81,p. 7008 - 7022

71
[ 1774-47-6 ]
[ 98977-36-7 ]
tert-butyl 1-oxa-5-azaspiro[2.5]octane-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%		To a solution of potassium tert-butoxide (2.20 g, 19.6 mmol) in DMSO (17 mL), trimethylsulfoxonium iodide (4.80 g, 21.8 mmol) was added in portions. The mixture was stirred at r.t. for 1.5 h. DME (4.5 mL) was added and it was cooled to 0-5 C. A solution of tert-butyl 3-oxopiperidine-i-carboxylate (3.0 g, 15.1 mmol) in a mixture of DME (4.5 mL) and DMSO (1.5 mL) was added dropwise. The reaction mixture wasstirred at 0-5 C for 1 h. It was diluted with water and ethyl acetate. The phases were separated and the aqueous phase was back extracted with additional ethyl acetate. The organic phases were combined, washed with water, dried over MgSO4 and concentrated under vacuum to give the title compound (2.36 g, 74% yield).
47%		j00509J To a stirred solution of trimethylsulfoxonium iodide (650 mg, 2.50 mmol) in DMSO (15 mL) was added 60 % NaH (138 mg, 3.01 mmol) stirred for 30 mm at RT. 1 (500 mg, 2.50 mmol) was added. The reaction mixture was stirred at RT for 12 h. Upon complete consumption of starting material, the reaction mixture was poured into water (25 mL), extracted with CH2C12 (2 x 25 mL). The organic extracts were washed with saturated NaHCO3 (25 mL), water (25 mL), brine (25 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford 1.46 (250 mg, 47%) as a brown gummy liquid.?HNIVIR (400 IVIHz, CDC13): (5: 3.46-3.43 (m, 3H), 3.36-3.33 (m, 1H), 2.75 (br s, 1H), 2.66 (d, J= 4.4 Hz, 1H), 1.86- 1.80 (m, 1H), 1.74 - 1.60 (m, 3H), 1.45 (s, 9H).
41%		Trimethylsulfoxonium iodide (1.1 g, 5.0 mmol) was dissolved in DMSO (5 mL) and stirred at room temperature for 1 h. NaH (0.24 g, 6 mmol) was added and the solution was stirred at 0C under nitrogen atmosphere for 1.3 h. To this mixture <strong>[98977-36-7]tert-butyl 3-oxopiperidine-1-carboxylate</strong> (1.1 g, 5 mmol) was added and then left at room temeperature overnight. The mixture was poured into ice and extracted with ether. The organic phase was separated, washed with water and then brine, dried over and concentrated under reduced pressure. The residue purified by silica flash chromatography with 5 to 50% ethyl acetate in cyclohexane to afford tert-butyl 1-oxa-5-azaspiro[2.5]octane-5-carboxylate (441 mg, 41% yield) as a white solid. MS found for C11H19NO3 as (M+H)+ 214.26.

35.96%

With potassium tert-butylate; In 1,2-dimethoxyethane; at 80℃; for 16h;

[00528] To the solution of 147-1 (2.00 g, 10.04 mmol, 1.00 eq) in DME (40.00 mL) was added t-BuOK (1.13 g, 10.04 mmol, 1.00 eq) and trimethylsulfoxonium iodide (2.21 g, 10.04 mmol, 1.00 eq). Then the mixture was stirred at 80 C for 16 hr. TLC showed some material remained and new spots were formed. The mixture was quenched with H20 (20 mL) and extracted with EtOAc (40 mL x3). The combined organic layers were washed with brine (20 mL), dried over Na2S04, filtered, and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography to give 147-2 (770.00 mg, 3.61 mmol, 35.96% yield) as a colorless oil. 1HNMR (400MHz, CHLOROFORM-_ 3.50 - 3.40 (m, 3H), 3.39 - 3.31 (m, 1H), 2.76 (br s, 1H), 2.66 (d, J= 4.5 Hz, 1H), 1.89 -1.78 (m, 1H), 1.77 -1.62 (m, 3H), 1.45 (s, 9H).

Reference： [1]Patent: WO2017/67664,2017,A1 .Location in patent: Page/Page column 200
[2]Patent: WO2019/89693,2019,A1 .Location in patent: Paragraph 00509
[3]Patent: WO2016/196776,2016,A2 .Location in patent: Paragraph 001042
[4]Patent: WO2018/204532,2018,A1 .Location in patent: Paragraph 00528

72
[ 1774-47-6 ]
[ 3695-84-9 ]
[ 479617-68-0 ]

Reference： [1]Journal of Organic Chemistry,2017,vol. 82,p. 9537 - 9549

73
[ 4969-01-1 ]
[ 1774-47-6 ]
1,6,9-trioxadispiro[2.1.4.3]dodecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53.6%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃; for 16h;Inert atmosphere;	A solution of 1 ,4-dioxaspiro[4.5]decan-7-one (280 g, 1793 mmol) in dimethyl sulfoxide (1 .5 L) under nitrogen at 20C was treated with trimethylsulfoxonium iodide (395 g, 1793 mmol) and potassium fe/f-butoxide (221 g, 1972 mmol), and the reaction mixture was stirred for 16 hours before being diluted with water and extracted with ethyl acetate (3 X 2 L). The combined organic extracts were washed with brine (2 X 500 ml), dried over Na2S04, filtered, concentrated under reduced pressure and purified by silica gel column chromatography (15% ethyl acetate/petroleum ether) to afford the title compound (170 g, 962 mmol, 53.6% yield) as a colorless oil. GCMS (m/z) 141 .2, 170.2.

Reference： [1]Patent: WO2017/199199,2017,A1 .Location in patent: Page/Page column 20; 21

74
[ 1774-47-6 ]
[ 53100-44-0 ]
(S)-2-((tert-butoxycarbonyl)amino)-6-(dimethyl(oxo)-λ6-sulfanylidene)-5-oxohexanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step A: Preparation of (S)-2-((tert-butoxycarbonyl)amino)-6-(dimethyl(oxo)- 6- sulfanylidene)-5-oxohexanoic acid (2) (0254) A solution of KOtBu (1.0 M in THF, 1.0 equiv) was added to a 0C solution of Boc-Pyr-OH (5.0 g, 1.0 equiv)) in DMF (10 mL) over 1 hr. In a separate flask, a solution of KOtBu (1.0 M in THF, 1.1 equiv) was added over 1 hr to a 0C slurry of trimethylsufoxonium iodide (1.2 equiv) in DMF (22 mL); the resulting mixture was stirred for 30 min after the end of addition. The thin slurry formed from addition of KOtBu to Boc-Pyr-OH was added over 1 hr to the suspension of sulfur ylide at 0C. The mixture was stirred for 24 hr while it warmed to ambient temperature, to give a thin slurry of sulfur ylide 2, which was used directly in the next step. M.S. (ESI): 322 (M+H)+

Reference： [1]Patent: WO2017/136254,2017,A1 .Location in patent: Page/Page column 28

75
[ 1774-47-6 ]
[ 144978-12-1 ]
ethyl (R)-2-((tert-butoxylcarbonyl)amino)-6-(dimethyl(oxo)-λ⁶-sulfanylidene)-5-oxohexanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		DMSO (240 mL) was added to a solution of trimethylsulfoxonium iodide (41 g, 186.3 mmol) and potassium tert-butoxide (20 g, 178.2 mmol) in THF (200 mL), reacted at 25C for 2 h, then cooled to -15C. A solution of <strong>[144978-12-1]1-(tert-butyl) 2-ethyl (R)-5-oxopyrrolidine-1,2-dicarboxylate</strong> (40 g, 155.5 mmol) in THF (120 mL) was added dropwise to the reaction system, then reacted for 3 h. After completion of the reaction, it was quenched with a saturated solution of ammonium chloride (200 mL), extracted with ethyl acetate (200 mL*3), and the organic layers were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain the crude product (50 g).

Reference： [1]Patent: EP3281942,2018,A1 .Location in patent: Paragraph 0130; 0131

76
[ 22929-52-8 ]
[ 1774-47-6 ]
[ 185-61-5 ]

Yield	Reaction Conditions	Operation in experiment
13%		To a mixture of trimethylsulfoxonium iodide (30.6 g, 150 mmol) in THF (100 mL) was added NaH (5.98 g, 60percent in miniral oil, 150 mmol) in portions at 0°C under N2. The mixture was stirred at 0°C for 30 mins. Dihydrofuran-3(2H)-one (10 g, 116 mmol) in DMSO (100 mL) was added dropwise at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The mixture was poured into ice-water (500 mL) in portions, extracted with DCM (2 x 500 mL). The combined organic phase was washed with brine (500 mL), dried over Na2S04, filtered and concentrated at 30°C. The residue was purified by Combi-flash (EtOAc in PE, 0percent~40percent) to afford J-l (1.5 g, 13 percent) as an oil. 1H NMR (400 MHz, CDC13) delta 4.11-3.90 (m, 3H), 3.66 (d, / = 10.0 Hz, 1H), 3.03 (d, / = 4.4 Hz, 1H), 2.94 (d, / = 4.0 Hz, 1H), 2.34-2.23 (m, 1H), 2.00-1.88 (m, 1H).

Reference： [1]Patent: WO2018/75699,2018,A1 .Location in patent: Paragraph 00378; 00391; 00449

77
[ 1774-47-6 ]
[ 30015-90-8 ]
[ 13861-75-1 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4540 - 4544

78
[ 2058-72-2 ]
[ 1774-47-6 ]
[ 1529769-50-3 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4540 - 4544

79
[ 1774-47-6 ]
[ 91-56-5 ]
[ 13861-75-1 ]

Reference： [1]Organic Letters,2018,vol. 20,p. 4540 - 4544

80
[ 77356-14-0 ]
[ 1774-47-6 ]
[ 27441-81-2 ]

Yield	Reaction Conditions	Operation in experiment
55%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;	General procedure: t-BuOK (80.0 g, 0.713 mol) was added in one portion to a stirred saturated solution of Me3SO+I- (196 g, 0.892 mol) in DMSO (600 mL) under argon atmosphere, and the mixture was stirred at r.t. until homogeneous (ca. 1 h). A solution of the corresponding ketone (0.594 mol) in THF (600 mL) was added dropwise to the stirred mixture at 15 Cfor 1 h, then the mixture was stirred for 0.5 h, diluted with H2O (1.5 L) and extracted with t-BuOMe (4 × 750 mL). The organic layer was washed with cold H2O (4 × 250 mL), dried over Na2SO4 and evaporated in vacuo. The residue was dissolved in hexanes (750 mL) and washed with cold brine (4 × 150 mL). The organic phase was separated and evaporated in vacuo to give the corresponding oxiranes.

Reference： [1]Synthesis,2018,vol. 50,p. 3696 - 3707

81
[ 912444-89-4 ]
[ 1774-47-6 ]
4-tert-butyl 1-ethyl 4-azabicyclo[5.1.0]octane-1,4-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
55%		To a suspension of NaH (21.2 g, 0.318 mol, 60% dispersion in mineral oil) in DMSO (650 mL), S,S,S-trimethylsulfoxonium iodide (72.9 g, 0.331 mol) was added in small portions and stirred at rt for 1 h until gas evolution ceased. A solution of <strong>[912444-89-4]1-tert-butyl 4-ethyl 2,3,6,7-tetrahydro-1H-azepine-1,4-dicarboxylate</strong> (9) (34.3 g, 0.127 mol) in DMSO (150 mL) was added dropwise and the reaction mixture was stirred at 50 C overnight. The resulting solution was cooled to rt, poured into ice-cold H2O (1 L) and extracted with t-BuOMe (3×700 mL). The combined organic extracts were washed with brine (3×500 mL), dried over anhydrous Na2SO4 and evaporated under reduced pressure. The product was purified by column chromatography (gradient hexane to hexane - t-BuOMe (7:3) as eluent). Yield: 19.8 g (55 %); colourless oil. 1H NMR(500 MHz, CDCl3): delta 4.14 - 4.06 (m, 2H), 3.98 - 3.78 (m, 2H), 3.10 (s, 1H), 2.96 (s, 1H), 2.77 (dd, J=15.3, 6.4 Hz, 1H), 2.36 (dt, J=14.1, 6.5 Hz, 1H), 1.75 - 1.65 (m, 1H), 1.49 (dd, J=9.2, 4.3 Hz, 1H), 1.43 (s, 9H), 1.37 - 1.26 (m, 2H), 1.23 (t, J=7.1 Hz, 3H), 0.77 (t, J=6.6, 4.3 Hz, 1H). 13C NMR(126 MHz, CDCl3): delta 175.4, 155.1, 79.3, 60.6, 47.6, 47.2, 32.7, 32.4, 28.4, 27.7, 26.9, 24.7, 14.2. MS (APCI): m/z = 284 [M+H]+. Anal. Calcd. for C15H25NO4: C 63.58; H 8.89; N 4.94. Found: C 63.86; H 8.58; N 5.13.

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4611 - 4615

82
[ 14533-86-9 ]
[ 1774-47-6 ]
methyl (1RS,2SR)-1-cyano-2-phenylcyclopropane-1-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 1087 - 1092

83
[ 6552-63-2 ]
[ 1774-47-6 ]
C₁₇H₁₅ClO₂ [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 2307 - 2311

84
[ 36823-88-8 ]
[ 1774-47-6 ]
4-trifluoromethoxyphenylsulfoxonium ylide [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 1504 - 1509
[2]Organic Letters,2019,vol. 21,p. 1125 - 1129
[3]Organic Letters,2019,vol. 21,p. 872 - 875

85
[ 4619-20-9 ]
[ 1774-47-6 ]
5-(hydroxymethyl)-5-(p-tolyl)dihydrofuran-2(3H)-one [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 5533 - 5537

86
[ 181269-69-2 ]
[ 1774-47-6 ]
tert-butyl 4-methyl-1-oxa-6-azaspiro[2.5]octane-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium tert-butylate; In 1,2-dimethoxyethane; dimethyl sulfoxide; at 0 - 5℃; for 1h;	To a solution of potassium tert- butoxide (2 g, 18.3 mmol) in DMSO (16 ml_), trimethylsulfoxonium iodide (1467) (4 g, 18.3 mmol) was added in portions keeping the internal temperature between 20- 25 C and the mixture was then stirred at r.t. for 1.5 h. DME (4.5 ml.) was added and the solution was cooled to 0-5 C. Then, a solution of tert- butyl 3-methyl-4- oxopiperidine-1-carboxylate (3 g, 14 mmol) in a mixture of DME (4.5 ml.) and DMSO (1.5 ml.) was added dropwise keeping the internal temperature between 0-5 C and the reaction mixture was further stirred for 1 h. Water and EtOAc were added, the phases were separated and the aq. phase was extracted twice with EtOAc. The organic phases were combined, washed with water (x4), dried over MgS04 and concentrated under vacuum to give the title compounds as a racemic mixture (2.88 g, 90% yield).

Reference： [1]Patent: WO2019/180188,2019,A1 .Location in patent: Page/Page column 339

87
[ 1774-47-6 ]
[ 79432-87-4 ]
rac-methyl (1R,2R)-2-(3-bromophenyl)cyclopropane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; mineral oil; at 20 - 50℃;Inert atmosphere;	Under argon, NaH (60 %, 680 mg, 17.0 mmol) was initially charged in DMSO (30 mL) and trimethylsulphoxonium iodide (3.74 g, 17.0 mmol) was added in one portion at rt. After the evolution of gas had ceased, compound P16a (3.15 g, 13.1 mmol), dissolved in DMSO (10 mL), was slowly added drop-wise. After stirring overnight at 50C, the mixture was partitioned between EA and water. The aq. layer was extracted with EA. The combined organic layer was dried over Na2S04, filtered, concentrated and purified by FCC (EA:PE = 1 :20) to give compound P16 as a colorless oil

Reference： [1]Patent: WO2020/2611,2020,A1 .Location in patent: Page/Page column 55-56

88
[ 6136-68-1 ]
[ 1774-47-6 ]
3-(2-methyloxetan-2-yl)benzonitrile [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2020,vol. 59,p. 7521 - 7527
Angew. Chem.,2020,vol. 132,p. 7591 - 7597,7

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1774-47-6	MDL No. :	MFCD00011899
Formula :	C₃H₉IOS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BPLKQGGAXWRFOE-UHFFFAOYSA-M
M.W :	220.07	Pubchem ID :	74498
Synonyms :

Num. heavy atoms :	6
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	39.66
TPSA :	36.28 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.79 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.2
Log Po/w (WLOGP) :	-2.62
Log Po/w (MLOGP) :	1.01
Log Po/w (SILICOS-IT) :	-0.46
Consensus Log Po/w :	-0.17

[ CAS No. 1774-47-6 ] {[proInfo.proName]}

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[ 1774-47-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 1774-47-6 ]

Aliphatic Chain Hydrocarbons

Precautionary Statements-General

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

Log S (ESOL) :	-1.96
Solubility :	2.41 mg/ml ; 0.011 mol/l
Class :	Very soluble
Log S (Ali) :	-1.56
Solubility :	6.08 mg/ml ; 0.0276 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-0.97
Solubility :	23.5 mg/ml ; 0.107 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.23

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 1774-47-6 ] {[proInfo.proName]}

Quality Control of [ 1774-47-6 ]

Related Doc. of [ 1774-47-6 ]

Product Details of [ 1774-47-6 ]

Calculated chemistry of [ 1774-47-6 ]

Physicochemical Properties

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Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

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Application In Synthesis of [ 1774-47-6 ]

[ 1774-47-6 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 1774-47-6 ]

Aliphatic Chain Hydrocarbons

Precautionary Statements-General

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Response

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[ 1774-47-6 ]