[ CAS No. 593-71-5 ] {[proInfo.proName]}

Name: 593-71-5|Chloroiodomethane|97% stabilized with Copper chip
Brand: Ambeed
SKU: A482895
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Quality Control of [ 593-71-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 593-71-5 ]

Product Details of [ 593-71-5 ]

CAS No. :	593-71-5	MDL No. :	MFCD00001078
Formula :	CH₂ClI	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PJGJQVRXEUVAFT-UHFFFAOYSA-N
M.W :	176.38	Pubchem ID :	11644
Synonyms :

Calculated chemistry of [ 593-71-5 ]

Physicochemical Properties

Num. heavy atoms :	3
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	0.0
Num. H-bond donors :	0.0
Molar Refractivity :	24.68
TPSA :	0.0 Å²

Pharmacokinetics

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) :	-6.27 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.4
Log Po/w (XLOGP3) :	1.56
Log Po/w (WLOGP) :	1.62
Log Po/w (MLOGP) :	1.82
Log Po/w (SILICOS-IT) :	2.02
Consensus Log Po/w :	1.68

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	3.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.92
Solubility :	2.14 mg/ml ; 0.0121 mol/l
Class :	Very soluble
Log S (Ali) :	-1.17
Solubility :	11.9 mg/ml ; 0.0676 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.85
Solubility :	2.5 mg/ml ; 0.0142 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	3.28

Safety of [ 593-71-5 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P310+P330-P302+P352-P304+P340+P312-P305+P351+P338-P332+P313-P337+P313-P403+P233-P405-P501	UN#:	2810
Hazard Statements:	H301-H315-H319-H335	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 593-71-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 593-71-5 ]
Downstream synthetic route of [ 593-71-5 ]

[ 593-71-5 ] Synthesis Path-Upstream 1~11

1
[ 593-71-5 ]
[ 28556-81-2 ]
[ 1131-01-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With methyllithium; lithium bromide In diethyl ether at -78℃; for 0.5 h;	General procedure: To a cooled (–78°C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi–LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1] Chemical Communications, 2013, vol. 49, # 75, p. 8383 - 8385
[2] Synthesis (Germany), 2014, vol. 46, # 21, p. 2897 - 2909

2
[ 74-85-1 ]
[ 593-71-5 ]
[ 6940-76-7 ]

Reference： [1] Journal of the American Chemical Society, 1950, vol. 72, p. 2213

3
[ 593-71-5 ]
[ 1124-14-7 ]

Reference： [1] Patent: EP1364957, 2003, A1, . Location in patent: Page/Page column 23

4
[ 593-71-5 ]
[ 4747-72-2 ]
[ 19047-31-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With methyllithium; lithium bromide In diethyl ether at -78℃; for 1 h;	General procedure: To a cooled (–78°C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi–LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1] Chemical Communications, 2013, vol. 49, # 75, p. 8383 - 8385
[2] Synthesis (Germany), 2014, vol. 46, # 21, p. 2897 - 2909

5
[ 76-09-5 ]
[ 5419-55-6 ]
[ 593-71-5 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 2.83333 h; Stage #2: With hydrogenchloride In tetrahydrofuran; hexane; ethyl acetate at 0℃; Stage #3: at 0 - 20℃; for 0.666667 h;	(Production Example 1) Synthesis of 2-(chloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To the mixture of triisopropyl borate (15 ml, 65 mmol), chloroiodomethane (13 g, 72 mmol), and tetrahydrofuran (78 ml), n-butyllithium (a 1.6 M n-hexane solution, 41 ml, 65 mmol) was added dropwise at -78°C (an outer temperature) over 20 minutes, and then the obtained mixture was stirred at room temperature for 2.5 hours. The reaction mixture was cooled to 0°C (an outer temperature), and a 4 N hydrochloric acid-ethyl acetate solution was added dropwise thereto at the same temperature until the reaction mixture became neutral. At the same temperature, pinacol (7.7 g, 65 mmol) was added to the reaction mixture, and then the reaction mixture was stirred at room temperature for 40 minutes. The solvents were evaporated under reduced pressure, and then the obtained residue was distilled under reduced pressure (63-70°C, 11 mmHg), thereby obtaining the entitled compound (9.2 g, 52 mmol, 81percent). ¹H-NMR Spectrum (CDCl₃) δ(ppm): 1.30(12H, s), 2.97(2H, s)

Reference： [1] Patent: EP2062901, 2009, A1, . Location in patent: Page/Page column 12
[2] Chemical Biology and Drug Design, 2011, vol. 78, # 5, p. 757 - 763

6
[ 593-71-5 ]
[ 61676-62-8 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
46%	Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.5 h; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran at 20℃; for 24.17 h;	To a stirred solution of 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (1 1 .0 mL, 53.75 mmol) and chloroiodomethane (4.3 mL, 59.12 mmol) in anhydrous THF (100 mL), cooled to -78 °C, was added cold n-butyllithium solution (23.94 mL, 59.12 mmol) dropwise. After stirring for 30 min at this temperature, chlorotrimethylsilane (8.2 mL, 64.50 mmol) was added dropwise. After stiring for 10 min, the reaction mixture was allowed to return to room temperature and stirred for 24 h. Water (80 mL) was added and the mixture extracted with Ε∑0 (2 x 80 mL). The organic extracts were combined, washed with water (2 x 80 mL), dried over MgS04 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (Heptane/EtOAc 99:1 to 95:5).to yield 2-(chloromethyl)-4, 4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (4.35 g, 24.65 mmol, 46percent yield) as a colourless oil. NMR (400 MHz, DMSO-cfe, δ): 2.99 (s, 2H), 1 .32 (s, 12H).

Reference： [1] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17470 - 17473
[2] Angewandte Chemie, International Edition, 2009, vol. 48, # 34, p. 6317 - 6319[3] Angewandte Chemie, 2009, vol. 121, # 34, p. 6435 - 6437
[4] Patent: WO2017/46604, 2017, A1, . Location in patent: Paragraph 00339; 00346

7
[ 76-09-5 ]
[ 593-71-5 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
81%	Stage #1: With n-butyllithium; Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 2.83 h; Stage #2: With hydrogenchloride In tetrahydrofuran; hexane; ethyl acetate at 0℃; Stage #3: at 0 - 20℃; for 0.666667 h;	To a mixture of triisopropyl borate (15 ml, 65 mmol), chloroiodomethane (13 g, 72 mmol) and tetrahydrofuran (78 ml) was added dropwise n-buthyllithium (1.6M n-hexane solution, 41 ml, 65 mmol) at -78°C (external temperature) over 20 minutes. Then, the mixture was stirred at room temperature for 2.5 hours. After the reaction mixture was cooled at 0°C (external temperature), to the mixture was added dropwise a 4N hydrochloric acid-ethyl acetate solution in order to neutralize at the same temperature. To the reaction mixture was added pinacol (7.7 g, 65 mmol) at the same temperature, and then, the reaction mixture was stirred at room temperature for 40 minutes. After the solvent was distilled off under reduced pressure, the resulting residue was distilled under reduced pressure (63-70°C, 11 mmHg) to obtain the title compound (9.2 g, 52 mmol, 81percent). ¹H-NMR Spectrum (CDCl₃) δ (ppm): 1.30 (12H, s) , 2.97(2H, s).

Reference： [1] Patent: EP1867650, 2007, A1, . Location in patent: Page/Page column 41

8
[ 593-71-5 ]
[ 82034-46-6 ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: With sodium ethanolate In N,N,N,N,N,N-hexamethylphosphoric triamide at 20℃; for 24 h; Large scale Stage #2: at 20℃; for 2 h; Large scale	To 50L reactor, add 1.9 kg intermediate 4, hexamethylphosphoric acid triamide 19L, sodium ethoxide 0.26 kg. React under the condition of room temperature for 24 hours. Add chloroiodomethane 1.4 kg. Stir for 2 hours. The reaction liquid quickly add 570L in water, separate out a large amount of yellow solid, filtering. The filter cake is added to the chloroform 5.7L dissolved, for sequentially 0.3M sodium thiosulfate solution 1.9L, 0 . 4M sodium bicarbonate solution, 1.9L saturated salt water 1.9L washing liquid, anhydrous sodium sulfate drying, decolorized with active carbon. Filtered, concentrated under reduced pressure to dryness; anhydrous ethanol is added 13.3L, heating to reflux, the solid is completely dissolved, gradually cooling crystallization, filtration. 40 °C blast drying, to obtain white solid 1.6 kg, yield 89percent.

Reference： [1] Patent: CN106554383, 2017, A, . Location in patent: Paragraph 0025; 0031; 0032

9
[ 593-71-5 ]
[ 127132-32-5 ]
[ 152438-62-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	at -78℃; for 1 h;	LDA (169 mL, 163 mmol) was added dropwise at 78 °C through a cannula to a mixture of iodochloromethane (9.45 mL, 130 mmol) and ethyl N-[(1,1-dimethylethyl)oxy]carbonyl}-O-(phenylmethyl)-L-tyrosinate (prepared as described in J. Med. Chem. 1990, 33, 1620) also at 78 °C. The resulting dark solution was stirred for one hour at 78 °C, then 50 mL of a 1:1 acetic acid:tetrahydrofuran solution was added slowly and the reaction was warmed to ambient temperature, poured onto a mixture of ice water and ethyl acetate, and the aqueous solution was extracted with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The brown solid was suspended in cold ether and filtered to give the title compound (3.17 g). The filtrate was concentrated under reduced pressure to give an additional 7.4 g of slightly impure title compound (10.57 g, 80percent yield). 1H NMR (400 MHz, CDCl3) δ 1.40 (s, 9H), 2.80-3.21 (m,2H), 3.87-4.25 (m, 2H), 4.42-4.72 (m, 1H), 5.03 (s, 2H), 6.81-7.17(m, 4H), 7.29-7.57 (m, 5H); LC/MS (m/z) ES⁺=427 (M + 23).

Reference： [1] Tetrahedron Letters, 1997, vol. 38, # 18, p. 3175 - 3178
[2] European Journal of Medicinal Chemistry, 2013, vol. 63, p. 202 - 212
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 15, p. 3496 - 3500

10
[ 50651-75-7 ]
[ 593-71-5 ]
[ 258516-84-6 ]

Reference： [1] Patent: US2015/111858, 2015, A1, . Location in patent: Paragraph 0069
[2] Patent: WO2016/77346, 2016, A1, . Location in patent: Paragraph 0101

11
[ 593-71-5 ]
[ 90084-26-7 ]
[ 84110-34-9 ]

Reference： [1] Organometallics, [2] Organometallics, 1985, vol. 4, p. 1687 - 1689

[ 593-71-5 ] Synthesis Path-Downstream 1~88

1
[ 593-71-5 ]
[ 98045-03-5 ]
[ 70606-85-8 ]

Reference： [1]Journal of Medicinal Chemistry,1979,vol. 22,p. 657 - 661

2
[ 106-98-9 ]
[ 593-71-5 ]
[ 3333-52-6 ]
1-Chloro-3-iodo-pentane [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 770 - 774

3
[ 592-41-6 ]
[ 593-71-5 ]
[ 3333-52-6 ]
[ 74962-48-4 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 770 - 774

4
[ 593-71-5 ]
[ 109-67-1 ]
[ 3333-52-6 ]
1-chloro-3-iodohexane [ No CAS ]
2-methyl-2-cyano-4-iodoheptane [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 770 - 774

5
[ 593-71-5 ]
[ 111-66-0 ]
[ 3333-52-6 ]
[ 74962-49-5 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1980,vol. 53,p. 770 - 774

6
[ 593-71-5 ]
[ 624-48-6 ]
[ 826-34-6 ]
[ 826-35-7 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1983,vol. 56,p. 1592 - 1597

7
[ 593-71-5 ]
[ 80-48-8 ]
[ 24124-59-2 ]
[ 117184-50-6 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 5783 - 5785
[2]Journal of Organic Chemistry,1988,vol. 53,p. 5783 - 5785

8
[ 593-71-5 ]
[ 52373-72-5 ]
[ 85364-10-9 ]

Yield	Reaction Conditions	Operation in experiment
30%	With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; for 0.333333h;Inert atmosphere;	To methyl (R)-(+)-2,2-dimethyl-l,3-dioxolane-4-carboxylate (5 g, 30.5925 mmol, 1 eq) and chloroiodomethane (5.757 mL, 13.4898 g, 76.4812 mmol, 2.5 eq) in 70 ml of dry THF, cooled at -78C, were added lithium diisopropylamide (38.2406 mL, 76.4812 mmol, 2.5 eq) over 10 minutes and kept stirring for additional 10 minutes before addition of 20 ml a solution of acetic acid in 120ml of THF and finally 50ml of water. The mixture was poured in a stirred biphasic solution of 600ml of ethyl acetate and 350ml of sodium hydroxide IN. The pH was basified by addition of 50ml of sodium hydroxide IN.Aqueous layers were extracted by 600ml of ethyl acetate. Organic layers were washed by brine, dried (MgSC^), and concentrated in vacuo. The resulting brown oil was purified two successive chromatography on silica gel (DCM 100%) yielding the title compound as a pale yellow oil (1.6g, 30%). 1H NMR delta: 4.62 (dd, J 7.8 Hz, J 5.1 Hz, 1 H), 4.46 (dd, J22.0 Hz, J 17.1 Hz, 2 H), 4.26 (t, J 8.9 Hz, 1 H), 4.09 (dd, J 9.0 Hz, J 5.0 Hz, 1 H), 1.50 (s, 3 H), 1.39 (s, 3 H).

Reference： [1]Patent: WO2015/86527,2015,A1 .Location in patent: Page/Page column 111
[2]Tetrahedron Letters,1996,vol. 37,p. 401 - 404

9
[ 593-71-5 ]
[ 28875-17-4 ]
[ 93371-30-3 ]

Yield	Reaction Conditions	Operation in experiment
81%	With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -75℃; for 0.166667h;

Reference： [1]Chen, Ping; Cheng, Peter T. W.; Spergel, Steven H.; Zahler, Robert; Wang, Xuebao; Thottathil, John; Barrish, Joel C.; Polniaszek, Richard P. [Tetrahedron Letters, 1997, vol. 38, # 18, p. 3175 - 3178]

10
[ 593-71-5 ]
[ 58561-04-9 ]
[ 103542-47-8 ]

Yield	Reaction Conditions	Operation in experiment
50%	With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -75℃; for 0.166667h;

11
[ 593-71-5 ]
[ 127132-32-5 ]
[ 152438-62-5 ]

Yield	Reaction Conditions	Operation in experiment
80%	With lithium diisopropyl amide; at -78℃; for 1.0h;	LDA (169 mL, 163 mmol) was added dropwise at 78 C through a cannula to a mixture of iodochloromethane (9.45 mL, 130 mmol) and <strong>[127132-32-5]ethyl N-[(1,1-dimethylethyl)oxy]carbonyl}-O-(phenylmethyl)-L-tyrosinate</strong> (prepared as described in J. Med. Chem. 1990, 33, 1620) also at 78 C. The resulting dark solution was stirred for one hour at 78 C, then 50 mL of a 1:1 acetic acid:tetrahydrofuran solution was added slowly and the reaction was warmed to ambient temperature, poured onto a mixture of ice water and ethyl acetate, and the aqueous solution was extracted with ethyl acetate, the organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The brown solid was suspended in cold ether and filtered to give the title compound (3.17 g). The filtrate was concentrated under reduced pressure to give an additional 7.4 g of slightly impure title compound (10.57 g, 80% yield). 1H NMR (400 MHz, CDCl3) delta 1.40 (s, 9H), 2.80-3.21 (m,2H), 3.87-4.25 (m, 2H), 4.42-4.72 (m, 1H), 5.03 (s, 2H), 6.81-7.17(m, 4H), 7.29-7.57 (m, 5H); LC/MS (m/z) ES+=427 (M + 23).

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 3175 - 3178
[2]European Journal of Medicinal Chemistry,2013,vol. 63,p. 202 - 212
[3]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 3496 - 3500

12
[ 593-71-5 ]
[ 4522-04-7 ]
[ 102123-74-0 ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 3175 - 3178
[2]Tetrahedron Letters,1997,vol. 38,p. 3175 - 3178

13
[ 593-71-5 ]
[ 68695-48-7 ]
[ 229625-50-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	at 20℃; for 4h;Inert atmosphere;	Di-tert-butyl phosphate tetrabutylammonium salt (0.826 g, 1.83 mmol) was combined with chloroiodomethane (1.6 mL, 18.3 mmol) and was stirred at r.t. for 4 h during which time a precipitate formed. Tert-butyl methyl ether was then added and the mixture was vigorously stirred for 20 min resulting in the formation of a white precipitate. The precipitate was removed by filtration through a pad of Celite and the filtrate was concentrated. The resulting yellow oil was then taken up in tert-butyl methyl ether (16 mL) to precipitate additional salts. The mixture was filtered through a pad of Celite and the filtrate was concentrated and dried under vacuum to afford di-tert-butyl (chloromethyl) phosphate (0.457 g, 97% yield) as an oil: 1H NMR (500 MHz, CHLOROFORM-d) delta 5.62 (d, J=14.5 Hz, 2H), 1.50 (s, 18H).
91%	In benzene; at 20℃; for 20h;Darkness;	Compound 2 was prepared by using an alternative method. To a solution of compound (1) (11.1 mmol) in benzene (0.9 mL/mmol) was added chloroiodomethane (111 mmol). The reaction mixture was stirred at room temperature for 20 hours in the dark. The crude mixture was concentrated under reduced pressure and the oily residue was dissolved in diethyl ether. The precipitate was filtered off and the organic layer was washed with a saturated NaHCO3 solution and brine. The organic layer was dried over Na2SO4, concentrated under reduced pressure and purified by chromatography on silica (cyclohexane/EtOAc 9:1 then 8:2) to afford the expected compound as a colorless oil in 61% yield. ?H NMR (CDC13, 400MHz) oe (ppm) 5.64 (d,J=l2Hz, 2H), 1.51 (s, 18H).
49%	In benzene; at 20℃; for 3h;	Method 2: Tetrabutylammonium di-t-butyl phosphate is prepared by dissolving di-t-butyl phosphate [2Og, 94 mmol (obtained from di-t-butyl phosphite by the method of Zwierzak and Kluba, Tetrahedron, Vol. 27, 3163 (1971)] in methanolic tetrabutylammonium hydroxide (47 mL of IM solution, 47 mmol) . The reaction mixture has a temperature of 23C and pH of 4.33. The pH of the reaction mixture is adjusted to 6.5-7.0 by addition of methanolic tetrabutylammonium hydroxide (48 mL of IM solution, 48 iranol) over 0.2 h. The reaction mixture is stirred for 0.5 h at approximately 2betaC and then is concentrated under reduced pressure at a bath temperature below 40C. The crude residue is azeotroped three times by adding toluene (3x100 mL) and then the mixture is concentrated under reduced pressure. The crude residue is then triturated in cold hexanes (0C) for 1 h and then the solid is collected by filtration, washed with a minimum amount of cold hexanes and dried to give a first crop of tetrabutylammonium di-t-butyl phosphate as a white- solid.(24.0 g) . The mother liquor is concentrated under reduced pressure and then triturated in cold hexanes (20 mL) for Ih.The solid is collected by filtration, washed with a minimum amount of cold hexanes and dried to give a second crop of tetrabutylammonium di-t-butyl phosphate as a white solid. [(8.5g), 32.5 g total (77%)]. A solution of tetrabutylammonium di-t-butyl phosphate (218 g, 480 mmol) in benzene (200 mL) is added dropwise to stirred chloroiodomethane (800 g, 4535 mmol) over 1.5 h at rt. The reaction mixture is stirred an additional 1.5 h at rt and then is concentrated under reduced pressure. The oily residue is dissolved in Et2O and filtered to remove white solids that precipitates. The organic layer is washed with saturated NaHCO3 and H2O/brine (1/1) . The organic layer is then dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield a red brown oil (320 g) . The red brown oil is subjected to chromatography on silica gel (800 g) eluted with 20% EtOAc/Hexanes, 25% EtOAc/Hexanes then 30% EtOAc/Hexanes. The product containing fractions are concentrated under reduced pressure to yield a golden oil. The oil is diluted with CH2C12 (30 mL) , concentrated under reduced pressure and then dried under vacuum to yield the compound 3 (61.3g, 49% yield). IH NMR (Benzene-dbeta) delta5.20 (2H, d, J=15), 1.22 (18H, s) .

	In benzene; at 20℃; for 4h;Product distribution / selectivity;	Phosphate ester A (45.1 g, 0.1 mol) and chloroiodomethane B (200 g, 1.14 mol) were combined in 100 ml of benzene and the mixture was stirred at room temperature for four hours before benzene was removed under vacuum. Then, 500 ml of ethyl ether was added to the residue and insoluble solid was filtered away. Concentration of the filtrate provided di-tert-butyl chloromethyl phosphate, which was utilized in the next step without any purification
	In acetone; at 40℃;	Di-tert-butyl phosphate potassium salt (5 g, 20.14 mmole) is dissolved in methanol (15 g): to this solution at 0 C. a slight excess of concentrated HCl is slowly added with efficient stirring at 0 C. The addition of acid causes the precipitation of potassium chloride. The solid is then filtered and washed with methanol. The compound in the mother liquor is then converted to the ammonium form by adding an equal molar amount of tetrabuthylammonium hydroxide 1 M in methanol (20.14 mmole) while keeping the reaction cooled at 0 C. with efficient stirring. The resulting clear solution is placed under reduced pressure to give the intermediate product. The <strong>[68695-48-7]tetrabuthylammonium di-tert-butyl-phosphate</strong> dissolved in acetone is then added dropwise to 53.3 grams of chloroiodomethane (302.1 mmole) and stirred at 40 C. for 1-2 hours. The solvent and excess of chloroiodomethane are distilled off, the reaction mass suspended in TBME and then filtered. The filtrate is washed by a saturated solution of sodium bicarbonate and water and then placed under reduced pressure to substitute the solvent by acetone, i.e., to remove the solvent after which it is replaced with acetone. The chloromethyl di-tert-butyl phosphate 7-20% in acetone is used in the next step without further purifications (70-80% yield): 1H-NMR (CD3OD, 300 MHz) delta 1.51 (s, 12H), 5.63 (d, 2H, J=14.8). 31P-NMR (CD3OD, 300 MHz) delta -11.3 (s, 1P).
	In acetone; at 40℃;	Di-tert-butyl phosphate potassium salt (5 g, 20.14 mmole)Was dissolved in methanol (15 g) and to this solution at 0 C.,Slowly add a slight excess of concentrated HCl and perform efficient stirring at 0 C.The addition of acid causes the precipitation of potassium chloride.The solids are then filtered and washed with methanol.By adding an equimolar amount of tetrabutylammonium hydroxide 1 M (20.14 mmole) in methanol,Converting the compound in the mother liquor to the ammonium form,Meanwhile, the reaction is cooled to 0 C. and efficient stirring is carried out.The resulting clear solution is placed under reduced pressure to provide the intermediate product.Thereafter, 53.3 grams of chloroiodomethane (302.1 mmole)Tetrabutylammonium di-tert-butylphosphate dissolved in acetone was added dropwise,And stir at 40 C. for 1-2 hours.The solvent and excess chloroiodomethane were distilled off,The reaction mass is suspended in TBME and then filtered.The filtrate is washed with a saturated solution of sodium bicarbonate and water, then placed under reduced pressure and the solvent is replaced with acetone, ie the solvent is removed,Replace it with acetone.7 to 20% of chloromethyl di-tert-butyl phosphate in acetone is used in the next step without further purification (70 to 80% yield):

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 1360 - 1363
[2]Patent: WO2015/42375,2015,A1 .Location in patent: Paragraph 00442
[3]Patent: WO2006/118351,2006,A1 .Location in patent: Page/Page column 56-58
[4]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 3669 - 3672
[5]Patent: US2005/209246,2005,A1 .Location in patent: Page/Page column 37; 41; 43; 44; 45; 47; 57
[6]Journal of Medicinal Chemistry,2012,vol. 55,p. 2048 - 2056
[7]Patent: US9403772,2016,B2 .Location in patent: Page/Page column 38
[8]Journal of Medicinal Chemistry,2018,vol. 61,p. 6308 - 6327
[9]Patent: JP2015/17121,2015,A .Location in patent: Paragraph 0182-0184

14
[ 593-71-5 ]
[ 51987-73-6 ]
[ 102123-74-0 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 7344 - 7347

15
[ 4313-03-5 ]
[ 593-71-5 ]
1-chloro-octa-3,5-dien-2-ol [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2007,vol. 5,p. 318 - 323

16
[ 1005-61-4 ]
[ 593-71-5 ]
[ 38380-85-7 ]

Yield	Reaction Conditions	Operation in experiment
97%	With diethylzinc; In n-heptane; 1,2-dichloro-ethane; at 0 - 5℃; for 3h;	Preparation 28 1-Bromo-4-(cyclopropoxy)benzene To a 0 C. solution of 1-bromo-4-vinyloxy-benzene (31.75 g, 159.51 mmol) and chloroiodomethane (101.3 g, 574.2 mmol) in 1,2-dichloroethane (410 mL), slowly add diethylzinc (1 M in heptane, 380 mL) over 1 hr while maintaining the temperature below 5 C. Stir the white mixture at 0-5 C. for 2 hours. Quench the reaction slowly at 5 C. with aqueous saturated ammonium chloride (400 mL, exothermic) and separate the layers. Extract the aqueous layer with diethyl ether (2*200 mL). Combine the organic layers, wash with saturated ammonium chloride (400 ml), dry over sodium sulfate, filter, and concentrate under reduced pressure to give the title compound (33 g, 97%) as an oil: GCMS: 212.
94%		Diethylzinc (15 % in hexanes, 95.5 mL, 116 mmol) was added to a mixture of 1 -bromo-4-vinyloxybenzene (11.5 g, 58 mmol), chloro-iodomethane (41 g, 232 mmol) and dichloro ethane (180 mL) over 3 h at 0 0C. After 30 min NH4Cl (aq, sat, 200 mL) and of petroleum ether (300 mL) were added. The organic phase was collected and concentrated. The residue was dissolved in petroleum ether, filtered and concentrated to afford the sub-title compound (11.7 g, 94%).
94%		Diethylzinc (15 % in hexanes, 95.5 mL, 116 mmol) was added to a mixture of 1 -bromo-4-vinyloxybenzene (11.5 g, 58 mmol), chloroiodomethane (41g, 232 mmol) and dichloroethane (180 mL) over 3 h at 0 0C. After 30 min, NH4Cl (aq, sat, 200 mL) and petroleum ether (300 mL) were added. The organic phase was collected and concentrated. The residue was dissolved in petroleum ether, filtered and concentrated to afford the sub-title compound (11.7 g, 94%).

94%		To mixture of 1-bromo-4-vinyloxybenzene (11.5 g, 58 imnol), chloro- iodomethane (41g, 232 mmol) and dichloroethane (180 mL) was added diethylzinc (15 % solution in hexanes; 95.5 mL, 116 mmol) over 3 h at 0C. After 30 min stirring, NH4CI solution (200 mL, aq. sat. ) and light petrol (300 mL) was added. The organic phase was separated and concentrated in vacuo (8 bar, 50 C). The residue was redissolved in light petrol and the insoluble material was filtered off. The filtrate was concentrated to afford sub-title compound (11.7 g, 94%).
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0℃; for 3h;	c)39.0 g (176 mmol) 1-bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol /1 in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The organic phases are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE) C9H9BrO (M=213.1 g/mol)EI- MS: 212/214 [M]+Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In 1,2-dichloro-ethane; at 0℃; for 3h;	c) 39.0 g (176 mmol) 1 -Bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled to 0C. During 1 h 200 mL (200 mmol) diethylzinc solution (c = 1 mol/l in hexane) are added and stirring is continued for 2 h at 0C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH CI solution and extracted with TBME (2x). The organic phases are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). C9H9BrO (M = 213.1 g/mol)EI-MS: 212/214 [M]+ Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0℃; for 3h;	c) 39.0 g (176 mmol) 1-Bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/l in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The organic phases are combined, washed with brine, dried over MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). [0346] C9H9BrO (M=213.1 g/mol) [0347] EI-MS: 212/214 [M]+ [0348] Rt (TLC): 0.4 (silica gel, PE)
		c) 39.0 g (176 mmol) of 1-bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled down to 0 C.During 1 h 200 mL (200 mmol) diethylzinc solution (c = 1 mol/l in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2x). The org. phases are combined, washed with sat. aq. NaCl solution, dried with MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silicagel, PE).C9H9BrO (M= 213.1 g/mol)EI-MS: 212/214 [M]+ Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0℃; for 3h;	[0507] c) 39.0 g (176 mmol) of 1-bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled down to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/l in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The org. phases are combined, washed with sat. aq. NaCl solution, dried with MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). [0508] C9H9BrO (M=213.1 g/mol) [0509] EI-MS: 212/214 [M]+ [0510] Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In 1,2-dichloro-ethane; at 0℃; for 3h;	Example IX 1 -l3romo-4-(2-bromoethoxy)benzene 39.0 g (176 mmol) of 1-bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled down to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/L in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The org. phases are combined, washed with sat. aq. NaCl solution, dried with MgSO4, filtered and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE)c) 39.0 g (176 mmol) of 1-bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled down to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c=1 mol/L in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH4Cl solution and extracted with TBME (2×). The org. phases are combined, washed with sat. aq. NaCl solution, dried with MgSO4, filtered and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). [0407] C9H9BrO (M=213.1 g/mol) [0408] EI-MS: 212/214 [M]+ [0409] Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0℃;	a) 55.0 g (318 mmol) 4-bromophenol and 14.1 g (352 mmol) NaOH are added to 1 10 mL water. 41 .1 mL (477 mmol) dibromoethane are added slowly and the reaction mixture is stirred for 16 h under reflux. Afterwards the reaction mixture is extracted with DCM and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, CyH/EtOAc 4/1 ). b) 52.0 g (186 mmol) of 1 -bromo-4-(2-bromoethoxy)benzene is added to 300 mL THF and cooled down to 0 C. Within 30 min 25.0 g (223 mmol) KOtBu are added to this mixture in several portions. Cooling is removed and the reaction mixture is stirred at r.t. over night. The reaction is queched by the addition of water. The resulting mixture is extracted with EtOAc (2x). The org. phases are combined, washed with sat. aq. NaCI solution, dried with MgSO4, filtered and the solvent is removed in vacuo. The resulting product is used without further purification. c) 39.0 g (176 mmol) of 1 -bromo-4-vinyloxybenzene and 32.4 mL (441 mmol) chloroiodomethane are added to 500 mL dichloroethane and cooled down to 0 C. During 1 h 200 mL (200 mmol) diethylzinc solution (c = 1 mol/L in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 mL of a sat. aq. NH CI solution and extracted with TBME (2x). The org. phases are combined, washed with sat. aq. NaCI solution, dried with MgSO4, filtered and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE). C9H9BrO (M= 213.1 g/mol) EI-MS: 212/214 [M]+ Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In hexane; at 0 - 20℃; for 1.75h;Inert atmosphere;	To a solution of the intermediate compound 10 (10.05 mmol, 2 g) and chloroiodomethane (60.28 mmol, 4.4 mL) under argon at 05C was slowly added diethylzinc (1 M solution in hexanes, 30.1 mmol, 30.1 mL). The reaction mixture was stirred at 05C for 15 min and allowed to warm to room temperature for 90 min. saturated NH4CI (5 mL) was added and the mixture partitioned with Et20 (50 mL), and saturated NH4CI (50 mL). The organic layer was separated and washed with brine, dried over anhydrous magnesium sulphate, filtered and concentrated to give the desired compound (2.00 g, Yield: 93%) which was used in the next step without further purification. 1 H NMR (400 MHz, CDCI3) delta 7.40-7.36 (2H, m), 6.96-6.91 (2H, m), 3.73-3.68 (1 H, m), 0.80-0.76 (4H, m) LC-MS: tR = 3.92 [M+H]+ not ion (method 3).
	With diethylzinc; In 1,2-dichloro-ethane; at 0℃; for 2h;	c) 39.0 g (176 mmol) of 1-bromo-4-vinyloxybenzene and 32.4 ml (441 mmol) chloroiodomethane are added to 500 ml dichloroethane and chilled to 0 C. During 1 h 200 ml (200 mmol) diethylzinc solution (c=1 mol/l in hexane) are added and stirring is continued for 2 h at 0. The reaction is quenched by the addition of 200 ml of a sat. aq. NH4Cl solution and extracted with TBME (2×). The org. phases are combined, washed with sat. aq. NaCl solution, dried with MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE) [0418] C9H9BrO (M=213.1 g/mol) [0419] EI-MS: 212/214 [M]+ [0420] Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0℃; for 3h;	General procedure: c) 39.0 g (176 mmol) of 1 -bromo-4-vinyloxybenzene and 32.4 ml (441 mmol) chloroiodomethane are added to 500 ml dichloroethane and chilled to 0 C. During 1 h 200 ml (200 mmol) diethylzinc solution (c = 1 mol/l in hexane) are added and stirring is continued for 2 h at 0 C. The reaction is quenched by the addition of 200 ml of a sat. aq. NH CI solution and extracted with TBME (2x). The org. phases are combined, washed with sat. aq. NaCI solution, dried with MgSO4 and the solvent is removed in vacuo. The crude product is purified by column chromatography (silica gel, PE) C9H9BrO (M= 213.1 g/mol) EI-MS: 212/214 [M]+ Rf (TLC): 0.4 (silica gel, PE)
	With diethylzinc; In dichloromethane; toluene; at 0 - 18℃;Inert atmosphere;	To a solution of 1-bromo-4- (vinyloxy) benzene (75 g, 0.376 mol) in DCM (800 mL) was added CH2ICl (264.7 g, 1.504 mol) at 18 C. Then Et2Zn (750 mL, 1M in toluene) was added slowly at 0 C under N2. The reaction was warmed to 18 C and stirred for 12 h under N2. Then the reaction mixture was added slowly to aqueous NH4Cl (500mL) , extracted with PE (3 x 800 mL) , dried over Na2SO4and filtered. The filtrate was concentrated, and the resulting residue was purified by column chromatography over silica gel (PE) to afford the title compound.

Reference： [1]Patent: US2011/144091,2011,A1 .Location in patent: Page/Page column 13
[2]Patent: WO2006/77364,2006,A1 .Location in patent: Page/Page column 78
[3]Patent: WO2006/77367,2006,A1 .Location in patent: Page/Page column 127
[4]Patent: WO2005/123673,2005,A1 .Location in patent: Page/Page column 76-77
[5]Patent: US2012/157425,2012,A1 .Location in patent: Page/Page column 57
[6]Patent: WO2013/79668,2013,A1 .Location in patent: Page/Page column 63-64
[7]Patent: US2013/143876,2013,A1 .Location in patent: Paragraph 0345; 0346; 0347; 0348
[8]Patent: WO2013/92616,2013,A1 .Location in patent: Page/Page column 85; 86
[9]Patent: US2013/158004,2013,A1 .Location in patent: Paragraph 0507
[10]Patent: US2013/172316,2013,A1 .Location in patent: Paragraph 0406; 0407; 0408; 0409
[11]Patent: WO2013/98375,2013,A1 .Location in patent: Page/Page column 73; 74
[12]Patent: WO2013/149996,2013,A1 .Location in patent: Page/Page column 47
[13]Patent: US2014/100211,2014,A1 .Location in patent: Paragraph 0417-0420
[14]Patent: WO2014/56771,2014,A1 .Location in patent: Page/Page column 84
[15]Patent: WO2018/107415,2018,A1 .Location in patent: Page/Page column 50

17
[ 593-71-5 ]
[ 1124-14-7 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4 -bromostylene (1.83g) in dichloromethane (5 mL) was added diethylzinc (1 mol/L, 30 mL) under an argon atmosphere at 0C, and the-mixture was stirred at the same temperature for 10 minutes. Chloroiodomethane (4.3 mL) was added to the mixture, and the mixture was warmed to room temperature and stirred for 9 days. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure to give 4-cyclopropylbromobenzene. The obtained 4-cyclopropylbromobenzene was dissolved in tetrahydrofuran (25 mL) and cooled to -78C. To the solution was added dropwise tert-butyl lithium (1.45 mol/L pentane solution, 9.4 mL) under an argon atmosphere, and the mixture was stirred at -78C for 30 minutes. To the reaction mixture was added a solution of N,N-dimethylformamide (1.2 mL) in tetrahydrofuran (16 mL), and the mixture was warmed to 0C and stirred for 1 hour. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate = 12/1) to give 4-cyclopropylbenzaldehyde (0.72 g).1H-NMR (CDCl3) delta ppm: 0.60-0.75 (2H, m), 1.05-1.15 (2H, m), 1.80-1.95 (1H, m), 7.15-7.25 (2H, m), 7.7'0-7.80 (2H, m), 9.94 (1H, s)

Reference： [1]Patent: EP1364957,2003,A1 .Location in patent: Page/Page column 23

18
[ 593-71-5 ]
[ 68695-48-7 ]
[ 427899-56-7 ]

Yield	Reaction Conditions	Operation in experiment
	at 25℃; for 3.41667h;	Method 3: Iodochloromethane (974 g, 402 mL, 5.53 mol) at 25C is treated with tetrabutylammonium di-t-butylphosphate (250 g, 0.553 mol) . The phosphate is added portionwise over 10 minutes. The heterogeneous mixture becomes a clear pink solution after approximately 15 minutes. The mixture is stirred for three hours, and the iodochloromethane is then removed by rotary evaporation with a bath temperature of <30C. ? The residue is taken up in 1 L t-butyl methyl ether and stirred for- 15 minutes to precipitate tetrabutylammonium iodide by-product. Tetrabutylammonium iodide is removed by vacuum filtration through a sintered glass funnel. The filtrate is concentrated by rotary evaporation to an oil which contains a 5:1 mixture of 3" and undesired dimer impurity:3"The mixture can be purified by a silica gel chromatography to obtain 3 as pure compound in ~60% yield as an oil.

Reference： [1]Patent: WO2006/118351,2006,A1 .Location in patent: Page/Page column 58

19
[ 593-71-5 ]
[ 68373-14-8 ]
[ 76247-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium chloride; N-ethyl-N,N-diisopropylamine; In water; N,N-dimethyl-formamide;	EXAMPLE 25 Chloromethyl Penicillanate 1,1-Dioxide To a stirred solution of 24 g. of penicillanic acid 1,1-dioxide in 125 ml. of N,N-dimethylformamide was added 9.5 ml. of diisopropylethylamine, followed by 45 ml. of chloroiodomethane. Stirring was continued overnight and then the reaction mixture was added to 300 ml of water. The pH was adjusted to 8.5, and then the mixture was extracted with ethyl acetate. The extract was washed with water, followed by saturated sodium chloride solution, and then it was dried over sodium sulfate. The dried extract was concentrated to dryness in vacuo to give the crude product as a gum (8.9 g.). The crude product was combined with some additional material of comparable quality, and it was chromatographed on silica gel eluding with 1:1 ethyl acetatehexane. This afforded the title compound which showed only a single spot when assayed by thin-layer chromatography. The IR spectrum (KBr disc) showed an absorption at 1801 cm-1. The NMR spectrum (CDCl3) showed absorptions at 6.0 (d, 2H, J=6Hz), 5.7 (d, 1H, J=6Hz), 4.7 (t, 1H, J=3.5Hz), 4.5 (s, 1H), 3.55 (d, 2H, J=3.5Hz), 1.7 (s, 3H) and 1.5 (s, 3H) ppm.

Reference： [1]Patent: US4244951,1981,A

20
aqueous sodium chloride [ No CAS ]
[ 593-71-5 ]
[ 68373-14-8 ]
[ 76247-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In N-methyl-acetamide; ethyl acetate;	PREPARATION 3 Chloromethyl penicillanate 1,1-dioxide To a solution of penicillanic acid 1,1-dioxide (1.17 g, 5 mmol) in dimethylformamide (7.5 ml) was added triethylamine (0.98 ml, 7 mmol) and chloroiodomethane (2.18 ml, 30 mmol), and the mixture was stirred at room temperature for 4 hours. After dilution with ethyl acetate (30 ml), the mixture was washed with water (3*10 ml) followed by saturated aqueous sodium chloride (5 ml), dried, and evaporated in vacuo to leave the desired compound as a yellowish oil, which crystallized from ether-petroleum ether, melting point: 94-96 C. The NMR spectrum (CDCl3) showed signals at delta=1.47 (s, 3H; 2-CH3), 1.66 (s, 3H; 2-CH3), 3.53 (d, J=3 Hz, 2H; 6alpha-H and 6beta-H), 4.46 (s, 1H; 3-H), 4.68 (t, J=3 Hz, 1H; 5-H), and 5.85 (ABq, J=6 Hz, 2H; OCH2 Cl) ppm. Tetramethylsilane was used as internal reference.

Reference： [1]Patent: US4325960,1982,A

21
tetrabutylammonium penicillanate sulfone [ No CAS ]
[ 593-71-5 ]
[ 68373-14-8 ]
Chloromethyl penicillanic acid 1,1-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetra(n-butyl)ammonium hydroxide; In dichloromethane; water; ethyl acetate;	EXAMPLE 4 Chloromethyl penicillanic acid 1,1-dioxide A mixture of 4.66 g. of penicillanic acid 1,1-dioxide in 50 ml. of methylene chloride and 35 ml. of water was treated with sufficient tetrabutylammonium hydroxide (40% in water) to give a pH of 6.0. The methylene chloride layer was separated and the aqueous phase extracted with fresh methylene chloride (2*50 ml.). The organic layers were combined, dried over sodium sulfate and concentrated to give 10.1 g. of the desired intermediate. The above tetrabutylammonium penicillanate sulfone was added to 50 ml. of chloroiodomethane and the reaction mixture allowed to stir at ambient temperatures overnight. The reaction mixture was concentrated to half volume in vacuo, and chromatographed on 200 g. of silica gel using ethyl acetate/hexane as the eluent, 12 ml. cuts being taken every 30 sec. Fractions 41-73 were combined and concentrated to dryness to give 3.2 g. of the desired product. The NMR spectrum (CDCl3) showed absorption at 1.5 (s, 3H), 1.66 (s, 3H), 3.42 (d, 2H), 4.38 (s, 1H), 4.6 (t, 1H) and 5.7 (dd, 2H) ppm.

Reference： [1]Patent: US4381263,1983,A

22
[ 593-71-5 ]
[ 113-98-4 ]
[ 35131-81-8 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide;	A. Bis-(6beta-phenylacetamido-penicillanoyloxy)-methane To a stirred suspension of <strong>[113-98-4]potassium benzylpenicillin</strong>ate (22.3 g.) in dimethylformamide (110 ml.) is added chloroiodomethane (5.3 g.). After stirring for 48 hours at room temperature the mixture is diluted with ethyl acetate (330 ml.) and extracted with water (260 ml.), 2% aqueous sodium bicarbonate (60 ml.) and water (260 ml.). The organic phase is dried and evaporated to dryness in vacuo to yield the desired compound as an amorphous powder. The IR-spectrum (CHCl3) shows strong bands at 1780, 1675, 1505, 1290, 1135 and 982 cm-1. The NMR-spectrum (CDCl3) shows peaks at delta=1.45 (s), 3.63 (s), 4.39 (s), 5.60-5.80 (m), 5.85 (s), 6.20 (d) and 7.33 (s). (TMS being used as internal standard).

Reference： [1]Patent: US4554160,1985,A

23
[ 593-71-5 ]
[ 33494-81-4 ]
[ 13086-84-5 ]
[ 18281-42-0 ]
[ 229625-50-7 ]

Yield	Reaction Conditions	Operation in experiment
71%	silver carbonate; In acetonitrile; benzene;	Preparation of di-tert-butyl chloromethyl phosphate, 2: Silver di-t-butyl phosphate (6.34 g, 20 mmol), which was prepared by mixing di-t-butyl phosphate (obtained from di-t-butyl phosphite by the method of Zwierzak and Kluba, Tetrahedron, 1971, 27, 3163) with one equivalent of silver carbonate in 50% aqueous acetonitrile and by lyophilizing to dryness, was placed together with chloroiodomethane (35 g, 200 mmol) in benzene and stirred at room temperature for 18 hrs. The reaction mixture was filtered and the filtrate concentrated under reduced pressure. The residue was chromatographed on silica and eluted with 2:1 hexanes-ethyl acetate. Appropriate fractions were concentrated to dryness to obtain the subtitle compound 2 (3.7 g, 71% yield): 1H NMR (CDCl3) delta 5.63 (d, 2H, J=17), 1.51 (s, 18H); MS (MH+=259).

Reference： [1]Patent: US6235728,2001,B1

24
[ 593-71-5 ]
[ 178172-26-4 ]
[ 214193-11-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With diethylzinc In 1,2-dichloro-ethane at -15℃; for 19h;	1.1 Step 1. Cyclopropanation of 4,5-dehydro-L-proline ethyl ester: 4,5-Dehydro-L-proline ethyl ester (35.0 g, 0.145 mol) was added to a solution of neat Et2Zn (35.8 g, 0.209 mol) in 1 liter of 1,2-dichloroethane at -15°C. To this mixture was added a dropwise addition of ClCH2I (102 g, 0.58 mol) over 1 h and the mixture stirred at -15°C for 18 h. The reaction was quenched with saturated aqueous bicarbonate and the solvent was evaporated and the reaction was taken up in EtOAc, washed with brine and purified by silica gel chromatography using a stepwise gradient of from 20% EtOAc/hexanes to 50% EtOAc/hexanes to give 17.5 g (50%) of diastereomerically pure step 1 title compound.
41%	With diethylzinc In tetrahydrofuran; 1,2-dichloro-ethane at -15℃; for 18.5h;	89.C A solution of the title compound from Step B above (3.5 g) in 1,2 dichloroethane (75 ml) was cooled to -15 0C and Et2Zn (25 mL of a 1.0 M solution in THF) was added dropwise. To this mixture was added drop wise ClCH2I (4.5 ml) over 30 minutes. After stirring for 18 h at -15 0C the mixture was quenched with saturated aqueous bicarbonate and the solvent was evaporated and the reaction was taken up in ethyl acetate and washed with brine.The organic phase was dried over MgSO4, filtered and concentrated. The residue was purified by chromatography on silica (cyclohexane/EtOAc 4: 1) to afford the diastereomerically pure title compound (1.5 g, 41 %, MNa+ = 278).

Reference： [1]Current Patent Assignee: ASTRAZENECA PLC - EP2272825, 2015, B1 Location in patent: Paragraph 0140
[2]Current Patent Assignee: AMGEN INC - WO2006/116157, 2006, A2 Location in patent: Page/Page column 114-115

25
[ 593-71-5 ]
[ 68471-57-8 ]
[ 841302-36-1 ]

Yield	Reaction Conditions	Operation in experiment
50%		Step 6: 2-Aza-bicyclo[3.1.0]hexane-2-carboxylic acid benzyl ester To a cold (0 C.) solution of <strong>[68471-57-8]2,3-dihydro-pyrrole-1-carboxylic acid benzyl ester</strong> (example 4, step 5, 300 mg, 1.0 eq.) in diethyl ether was slowly added a solution of diethylzinc in hexanes (1M, 7 mL, 4.75 eq.), followed by chloroiodomethane (1.1 mL, 10 eq.). The reaction mixture was stirred 3 h at 0 C., allowed to warm up to room temperature and stirred an additional 3 h. The reaction mixture was partitioned between an aqueous solution of ammonium chloride and diethyl ether. The aqueous layer was extracted with diethyl ether and the combined organic layers were washed with brine, dried over sodium sulphate and evaporated in vacuo and purified on silica, eluding with a 1:1 to 1:3 gradient of cyclohexane/dichloromethane, to yield 160 mg (50%) of the desired product as colourless oil. MS (m/e): 218.5 (MH+, 100%)

Reference： [1]Patent: US2007/123525,2007,A1 .Location in patent: Page/Page column 19
[2]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 6476 - 6480

26
[ 593-71-5 ]
[ 90084-26-7 ]
[ 84110-34-9 ]

Reference： [1]Organometallics,1985,vol. 4,p. 1687 - 1689

27
[ 593-71-5 ]
[ 94242-85-0 ]
[ 82954-89-0 ]

Reference： [1]Organometallics,1985,vol. 4,p. 1687 - 1689

28
[ 593-71-5 ]
[ 189442-87-3 ]
[ 1065607-97-7 ]

Yield	Reaction Conditions	Operation in experiment
44.92%	With lithium diisopropyl amide; In tetrahydrofuran; at -78℃; for 0.666667h;	Lithium diisopropylamide (30.9 mL, 46.4 mmol) was added dropwise to a solution containing ethyl N-Boc-4-methylpiperidine-4-carboxylate (2.52 g, 9.28 mmol), and chloroiodomethane (6.55 g, 37.1 mmol) in THF (100 mL) at -78 0C over 30 minutes. After <n="84"/>addition, the reaction was stirred for 10 minutes, and then a solution of acetic acid (5 mL) in THF (45 mL) was added while keeping reaction mixture below -65 0C. The reaction was stirred for an additional 10 minutes and partitioned between ethyl acetate and brine, washed with saturated bicarbonate, concentrated and purified by silica gel (10%-20% ethyl acetate in hexanes) to afford tert-butyl 4-(2-chloroacetyl)-4-methylpiperidine-l-carboxylate (1.15 g, 44.92% yield).

Reference： [1]Patent: WO2008/118718,2008,A2 .Location in patent: Page/Page column 82-83

29
[ 593-71-5 ]
[ 33494-81-4 ]
[ 229625-50-7 ]
[ 427899-56-7 ]

Yield	Reaction Conditions	Operation in experiment
		Di-tert-butyl chloromethyl phosphate (3). In 50 mL of acetone was stirred (cloudy solution ) 2.68 g (12.7 mmol) of <strong>[33494-81-4]di-tert-butyl phosphate</strong> (2) on an ice bath. To the mixture was added 2.30 g (12.7 mmol) of tetramethylammonium hydroxide pentahydrate in10 mL water with stirring to give a clear solution. The solution was evaporated to a cloudy thick011 and dissolved in 50 mL of dimethoxy ethane. The cloudy dimethoxyethane was evaporated to cloudy semi-solid and placed under high vacuum until the residue formed a solid. The solid was slurried in 50 mL of refluxing dimethoxyethane and 2 g (141.7 mmol) of chloroiodomethane was added. An almost clear light yellow solution formed and refluxing was continued for 1 hour. A precipitate formed in about 5 minutes, which was yellow at first and then white in color. The hot mixture was filtered and the dimethoxyethane evaporated to give 1.90 g (58%) of a light yellow oil (3). NMR: 1H (300 MHz, CDCl3) delta 1.57 (s, 9H), 5.63 (d, 2H, J = 15 Hz); 31P NMR (300 MHz, CDCl3) delta -10.8 (s). The NMR showed about 10-15% bis-di-te/t-butyl methyl phosphate impurity that could not be removed by flash column chromatography (silica gel, ethyl acetate/hexane eluent), even with 100% ethyl acetate eluent. 1H (300 MHz, CDCl3) delta 1.5 (s, 18 H), 1.50 (s, 18H), 5.44 (t, 2H, J=12Hz); 31P NMR (300 MHz, CDCl3) delta -11.1 (s).

Reference： [1]Patent: WO2008/70149,2008,A2 .Location in patent: Page/Page column 63-64

30
[ 593-71-5 ]
[ 159635-22-0 ]
[ 1101840-72-5 ]

Yield	Reaction Conditions	Operation in experiment
54%		To a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in 1,2-dichloroethane (80 ml) at 0 C. was added chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of <strong>[159635-22-0]3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butyl ester</strong> (J. Org. Chem. 2001, 66, 2487) (4.19 g, 19.6 mmol) in 1,2-dichloroethane (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0 C. and then allowed to reach room temperature, stirring for a further 1 h. The reaction was then quenched by addition of saturated aq. ammonium chloride solution, separated, and the organic dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 2:8-1:1) afforded the title product (2.4 g, 54%) as a crystalline solid MS: 228.2 (MH+).
54%		a) 4-Hydroxy-6-aza-spiro[2.5]octane-6-carboxylic Acid tert-butyl esterMethod A; To a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in DCE (80 ml) at 0 C. was added chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of <strong>[159635-22-0]3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butyl ester</strong> (J. Org. Chem. 2001, 66, 2487) (4.19 g, 19.6 mmol) in DCE (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0 C. and then allowed to reach RT, stirring for a further 1 h. The reaction was then quenched by addition of sat. aq. ammonium chloride solution, separated, and the organic dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc/heptane 2:8?1:1) afforded the title product (2.4 g, 54%) as a crystalline solid. MS: 228.2 (MH+).
54%		To a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in 1,2- dichloroethane (80 ml) at 0C was aded chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of 3-hydroxy-4- methylene-piperidine-l-carboxylic acid tert-butyl ester (J. Org. Chem. 2001, 66, 2487) (4.19 g, 19.6 mmol) in 1,2-dichloroethane (10 ml) was aded, after which time the reaction was stirred for 0.5 h at 0C and then allowed to reach room temperature, stirring for a further 1 h. The reaction was then quenched by adition of sat. aq.ammonium chloride solution, separated, and the organic dried (Na2S04) and concentrated. Purfication by flash column chromatography (Si02; ethylacetate/heptane 2:8-1 :1) afforded the titled product (2.4 g, 54%) as a crystalline solid. MS: 228.2 (MH+).

54%

Method ATo a solution of diethylzinc (1.1 M solution in toluene, 37.5 ml, 0.04 mmol) in 1,2-dichloroethane (80 ml) at 0 C. was added chloroiodomethane (5.99 ml, 0.08 mmol) under Ar. This mixture was stirred for 15 minutes before a solution of <strong>[159635-22-0]3-hydroxy-4-methylene-piperidine-1-carboxylic acid tert-butyl ester</strong> (J. Org. Chem. 2001, 66, 2487) (4.19 g, 19.6 mmol) in 1,2-dichloroethane (10 ml) was added, after which time the reaction was stirred for 0.5 h at 0 C. and then allowed to reach room temperature, stirring for a further 1 h. The reaction was then quenched by addition of sat. aq. ammonium chloride solution, separated, and the organic dried (Na2SO4) and concentrated. Purfication by flash column chromatography (SiO2; ethyl acetate/heptane 2:8-1:1) afforded the titled product (2.4 g, 54%) as a crystalline solid. MS: 228.2 (MH+).

Reference： [1]Patent: US2009/23713,2009,A1 .Location in patent: Page/Page column 18
[2]Patent: US2010/22518,2010,A1 .Location in patent: Page/Page column 19
[3]Patent: WO2011/48032,2011,A1 .Location in patent: Page/Page column 46-47
[4]Patent: US2011/92698,2011,A1 .Location in patent: Page/Page column 20

31
[ 593-71-5 ]
[ 60456-21-5 ]
[ 1138676-30-8 ]

Yield	Reaction Conditions	Operation in experiment
42%		[00313] Step E: To a solution of (S)-methyl 2,2-dimethyl-1,3-dioxolane-4-carboxylate(1.3 g, 8.1 mmol) and chtorotodomethane (4.3 g, 24 mmol) in THF (50 mL) at -78 C was added a solution of LDA (16.2 mL, 24 mmol) in portions over 10 minutes. The reaction was stirred at -78 C for 10 minutes. To this mixture was added a 10% solution of acetic acid (50 mL) in THF at -78 C. After addition, the slurry was warmed to ambient temperature. The reaction was poured into EtOAc (200 mL) and the aqueous layer basified using 1 N NaOH. The organics were separated and washed with brine, dried over MgSO4 and concentrated in vacuo. The material was purified by chromatography using DCM as eluent to give (S)-2- chloro-1-(2,2-dimethyl-1,3-dioxolane-4-yl)ethanone (0.60 g, 3.4 mmol, 42% yield) as an oil.

Reference： [1]Patent: WO2009/42435,2009,A1 .Location in patent: Page/Page column 55

32
[ 76-09-5 ]
[ 5419-55-6 ]
[ 593-71-5 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
81%		(Production Example 1) Synthesis of 2-(chloromethyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane To the mixture of triisopropyl borate (15 ml, 65 mmol), chloroiodomethane (13 g, 72 mmol), and tetrahydrofuran (78 ml), n-butyllithium (a 1.6 M n-hexane solution, 41 ml, 65 mmol) was added dropwise at -78C (an outer temperature) over 20 minutes, and then the obtained mixture was stirred at room temperature for 2.5 hours. The reaction mixture was cooled to 0C (an outer temperature), and a 4 N hydrochloric acid-ethyl acetate solution was added dropwise thereto at the same temperature until the reaction mixture became neutral. At the same temperature, pinacol (7.7 g, 65 mmol) was added to the reaction mixture, and then the reaction mixture was stirred at room temperature for 40 minutes. The solvents were evaporated under reduced pressure, and then the obtained residue was distilled under reduced pressure (63-70C, 11 mmHg), thereby obtaining the entitled compound (9.2 g, 52 mmol, 81%). 1H-NMR Spectrum (CDCl3) delta(ppm): 1.30(12H, s), 2.97(2H, s)

Reference： [1]Patent: EP2062901,2009,A1 .Location in patent: Page/Page column 12
[2]Chemical Biology and Drug Design,2011,vol. 78,p. 757 - 763

33
[ 593-71-5 ]
[ 61676-62-8 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
46%		To a stirred solution of 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (1 1 .0 mL, 53.75 mmol) and chloroiodomethane (4.3 mL, 59.12 mmol) in anhydrous THF (100 mL), cooled to -78 C, was added cold n-butyllithium solution (23.94 mL, 59.12 mmol) dropwise. After stirring for 30 min at this temperature, chlorotrimethylsilane (8.2 mL, 64.50 mmol) was added dropwise. After stiring for 10 min, the reaction mixture was allowed to return to room temperature and stirred for 24 h. Water (80 mL) was added and the mixture extracted with Epsilon?0 (2 x 80 mL). The organic extracts were combined, washed with water (2 x 80 mL), dried over MgS04 and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel (Heptane/EtOAc 99:1 to 95:5).to yield 2-(chloromethyl)-4, 4, 5, 5-tetramethyl-1 ,3,2-dioxaborolane (4.35 g, 24.65 mmol, 46% yield) as a colourless oil. NMR (400 MHz, DMSO-cfe, delta): 2.99 (s, 2H), 1 .32 (s, 12H).

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 17470 - 17473
[2]Angewandte Chemie - International Edition,2009,vol. 48,p. 6317 - 6319
Angewandte Chemie,2009,vol. 121,p. 6435 - 6437
[3]Patent: WO2017/46604,2017,A1 .Location in patent: Paragraph 00339; 00346

34
[ 593-71-5 ]
[ 557-20-0 ]
[ 151907-79-8 ]
[ 1201187-23-6 ]

Yield	Reaction Conditions	Operation in experiment
35%		To <strong>[151907-79-8](1S,4R)-4-(tert-butoxycarbonylamino)cyclopent-2-enecarboxylic acid</strong> (2.70 g, 11.8 mmol, Preparation No.17) in DCM (170 mL) was slowly added diethylzinc (1.1 M in toluene, 54.0 mL, 59.4 mmol). The mixture was stirred for about 10 min at ambient temperature, cooled to about 0 C., and treated drop-wise with a solution of chloroiodomethane (4.30 mL, 59.4 mmol) in DCM (24 mL). The reaction mixture was allowed to warm to room temperature and was stirred for about 18 h. Saturated aqueous NH4Cl (10 mL) was added and the mixture was stirred for about 20 min. The layers were separated and the aqueous layer was further extracted with DCM (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with a gradient of 0-100% EtOAc/heptane to afford (1R,2S,4R,5S)-methyl 4-(ethoxycarbonylamino)bicyclo[3.1.0]hexane-2-carboxylate (0.95 g, 35%): LC/MS (Table 2, Method a) Rt=1.88 min; MS m/z: 228 (M+H)+.

Reference： [1]Patent: US2009/312338,2009,A1 .Location in patent: Page/Page column 129

35
[ 593-71-5 ]
[ 89678-08-0 ]
C₈H₉ClO₄ [ No CAS ]

Reference： [1]Tetrahedron Asymmetry,2009,vol. 20,p. 2105 - 2111

36
[ 20098-14-0 ]
[ 593-71-5 ]
[ 898909-53-0 ]

Yield	Reaction Conditions	Operation in experiment
		(a). Synthesis of bis-[5-oxy-adamantan-2-one]methane: Into 1 L three neck flask equipped with magnetic stirrer, pressure-equalizing addition funnel and reflux condensor under nitrogen atmosphere, 12.7 parts of sodium hydride (60% dispersion in mineral oil) was mixed with 125 mL of hexane and stirred for 3 mins. Stirring was stopped for 5 min and hexane decanted off. This process was repeated with additional 2*125 mL hexane and suspended in 125 mL of anhydrous tetrahydrofuran. Then 43 parts of 5-hydroxy-2-adamantanone was added portion wise over 2 min and the reaction mixture was heated at reflux for 90 mins. After the reaction mixture was cooled to room temperature and 62 parts of chloroiodomethane was added at once and the reaction mixture was heated at reflux for 22 hrs. The reaction mixture was cooled to 30 C. and 23.8 parts chloroiodomethane was added at once and heated at reflux for 48 hrs. The solution was cooled to room temperature and concentrated under reduced pressure and residue was extracted with 350 mL of dichloromethane. The organic layer was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the mixture was purified by chromatography on silica gel with 20% ethyl acetate-hexanes. The product fractions (TLC) were combined and solvent was evaporated under reduced pressure to give 12.72 parts of a white solid of the following structure confirmed by NMR.

Reference： [1]Patent: US2007/225498,2007,A1 .Location in patent: Page/Page column 35

37
[ 76-09-5 ]
[ 593-71-5 ]
[ 83622-42-8 ]

Yield	Reaction Conditions	Operation in experiment
81%		To a mixture of triisopropyl borate (15 ml, 65 mmol), chloroiodomethane (13 g, 72 mmol) and tetrahydrofuran (78 ml) was added dropwise n-buthyllithium (1.6M n-hexane solution, 41 ml, 65 mmol) at -78C (external temperature) over 20 minutes. Then, the mixture was stirred at room temperature for 2.5 hours. After the reaction mixture was cooled at 0C (external temperature), to the mixture was added dropwise a 4N hydrochloric acid-ethyl acetate solution in order to neutralize at the same temperature. To the reaction mixture was added pinacol (7.7 g, 65 mmol) at the same temperature, and then, the reaction mixture was stirred at room temperature for 40 minutes. After the solvent was distilled off under reduced pressure, the resulting residue was distilled under reduced pressure (63-70C, 11 mmHg) to obtain the title compound (9.2 g, 52 mmol, 81%). 1H-NMR Spectrum (CDCl3) delta (ppm): 1.30 (12H, s) , 2.97(2H, s).

Reference： [1]Patent: EP1867650,2007,A1 .Location in patent: Page/Page column 41

38
[ 593-71-5 ]
[ 73323-65-6 ]
[ 871716-67-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3172 - 3176

39
[ 593-71-5 ]
[ 145576-28-9 ]
ethyl spiro[2.5]octane-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0 - 20℃; for 19h;	Cap N-8 At 0 C., to a solution of ethyl 4-methylenecyclohexanecarboxylate (0.08 g) in DCE (1 mL) was added chloroiodomethane (0.110 mL, 1.522 mmol), followed by the addition of 1 N diethylzinc in hexane (0.761 mL, 0.761 mmol). The reaction was stirred at 0 C. for 1 hr, then stirred at rt for 18 hrs. The reaction mixture was diluted with EtOAc and 1 N HCl, the organic phase was washed with sat. NaCl, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was charged to a 25 g silica gel cartridge which was eluted with a 20 min gradient of 0-6% EtOAc in hexane to yield ethyl spiro[2.5]octane-6-carboxylate. 1H NMR (400 MHz, CDCl3) delta ppm 4.08-4.18 (2H, m), 2.32 (1H, tq, J=11.01, 3.53 Hz), 1.85-1.93 (2H, m), 1.53-1.74 (4H, m), 1.28-1.35 (2H, m), 1.22-1.28 (3H, m), 0.28 (2H, ddd, J=8.53, 5.52, 1.51 Hz), 0.17-0.25 (2H, m).
	With diethylzinc; In hexane; 1,2-dichloro-ethane; at 0 - 20℃; for 19h;	At 0 C, to a solution of ethyl 4-methylenecyclohexanecarboxylate (0.08 g) in DCE (1 mL) was added chloroiodomethane (0.110 mL, 1.522 mmol), followed bythe addition of 1 N diethylzinc in hexane (0.76 1 mL, 0.76 1 mmol). The reaction was stirred at 0 C for 1 hr, then stirred at rt for 18 hrs. The reaction mixture was diluted with EtOAc and 1 N HC1, the organic phase was washed with sat. NaC1, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was charged to a 25 g silica gel cartridge which was eluted with a 20 mm gradient of 0-6% EtOAc inhexane to yield ethyl spiro[2.5]octane-6-carboxylate. ?H NMR (400 MHz, CDC13) ppm 4.08-4.18(2 H, m), 2.32 (1 H, tq, J=11.01, 3.53 Hz), 1.85 - 1.93 (2 H, m), 1.53- 1.74 (4 H, m), 1.28 - 1.35 (2 H, m), 1.22 - 1.28 (3 H, m), 0.28 (2 H, ddd, J=8.53, 5.52, 1.51 Hz), 0.17 - 0.25 (2 H, m).

Reference： [1]Patent: US2013/183269,2013,A1 .Location in patent: Paragraph 1343; 1344
[2]Patent: WO2015/5901,2015,A1 .Location in patent: Page/Page column 543

40
[ 593-71-5 ]
[ 103-71-9 ]
[ 587-65-5 ]

Yield	Reaction Conditions	Operation in experiment
98%	With methyllithium lithium bromide In diethyl ether at -78℃;
98%	With methyllithium; lithium bromide In diethyl ether at -78℃; for 0.5h; chemoselective reaction;	Chemoselective Addition of Lithium Carbenoids to Isocyanates; General Procedure 1 (GP1) General procedure: To a cooled (-78°C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi-LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1]Pace, Vittorio; Castoldi, Laura; Holzer, Wolfgang [Chemical Communications, 2013, vol. 49, # 75, p. 8383 - 8385]
[2]Pace, Vittorio; Castoldi, Laura; Mamuye, Ashenafi Damtew; Holzer, Wolfgang [Synthesis, 2014, vol. 46, # 21, p. 2897 - 2909]

41
[ 593-71-5 ]
[ 18908-07-1 ]
[ 17641-08-6 ]

Yield	Reaction Conditions	Operation in experiment
94%	With methyllithium; lithium bromide; In diethyl ether; at -78℃; for 0.5h;	General procedure: To a cooled (-78C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi-LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1]Chemical Communications,2013,vol. 49,p. 8383 - 8385
[2]Synthesis,2014,vol. 46,p. 2897 - 2909

42
[ 593-71-5 ]
[ 50528-86-4 ]
[ 328-26-7 ]

Reference： [1]Chemical Communications,2013,vol. 49,p. 8383 - 8385

43
[ 593-71-5 ]
[ 3173-53-3 ]
[ 23605-23-4 ]

Yield	Reaction Conditions	Operation in experiment
97%	With methyllithium lithium bromide In diethyl ether at -78℃;
97%	With methyllithium; lithium bromide In diethyl ether at -78℃; for 1h; chemoselective reaction;	Chemoselective Addition of Lithium Carbenoids to Isocyanates; General Procedure 1 (GP1) General procedure: To a cooled (-78°C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi-LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

44
[ 593-71-5 ]
[ 4747-72-2 ]
[ 19047-31-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With methyllithium; lithium bromide; In diethyl ether; at -78℃; for 1h;	General procedure: To a cooled (-78C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi-LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1]Chemical Communications,2013,vol. 49,p. 8383 - 8385
[2]Synthesis,2014,vol. 46,p. 2897 - 2909

45
[ 593-71-5 ]
[ 45676-04-8 ]
1,1′-methylene bis(3-tert-butylimidazolium)diiodide [ No CAS ]
3-(tert-butyl)-1-(iodomethyl)-imidazolium iodide [ No CAS ]
3-(tert-butyl)-1-(chloromethyl)-imidazolium iodide [ No CAS ]

Reference： [1]Dalton Transactions,2013,vol. 42,p. 12861 - 12864

46
[ 593-71-5 ]
[ 84348-38-9 ]
[ 1129634-43-0 ]
[ 84348-39-0 ]

Yield	Reaction Conditions	Operation in experiment
	With diethylzinc; In n-heptane; dichloromethane; at -5 - 20℃; for 19.5h;	A. Cyclopropanation to Prepare 2 [0133] To a solution of DCM (1.5 L) and n-heptane (0.32 L) at ambient temperature was added diethyl zinc (800 mL, 1.0 M in n-heptane). The reaction mixture was cooled to 0 C., and a solution of compound 1 (45.0 g) in DCM (250 mL) was added over 10 min. Upon completion of the addition, the reaction mixture was cooled to -5 C. and chloroiodomethane (176 g) was charged via syringe pump over 3.5 h. The reaction mixture was stirred at -5 C. for an additional 16 h and was quenched by the slow addition (1 h) of 1N aqueous HCl (1.4 L). After warming to 20 C., the phases were separated, and the aqueous layer was back extracted with DCM (0.5 L). The combined organic layers were washed with 10% aqueous NaCl (1.2 L), the phases were separated, and the organic layer was concentrated in vacuo to provide a crude oil that was purified by flash chromatography on silica gel (50 ethyl acetate/n-heptane). The desired product was isolated as a mixture of compounds 2 and 3 (46.6 g, 67.5 wt % compound 2, 62% corrected yield.)

Reference： [1]Patent: US2013/324740,2013,A1 .Location in patent: Paragraph 0131; 0132; 0133

47
[ 593-71-5 ]
[ 84348-38-9 ]
[ 1129634-44-1 ]
C₁₁H₁₆INO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Hydrolysis/Iodolactonization to Prepare 4: [0137] A mixture of compounds 2 and 3 (161.80 g, 59 wt % compound 2) was dissolved in MeOH (1.2 L). Water was added, the mixture was cooled to 15 C. and solid LiOH.H2O (32.8 g) was charged. The reaction mixture was warmed to 25 C. and stirred for 13.5 h. The reaction mixture was then concentrated in vacuo to remove the MeOH, and DCM (1 L) and water (200 mL) were added. The resulting mixture was cooled to 10 C., and 2 N aqueous HCl (375 mL) was added. Following separation of the phases, the aqueous layer was extracted with DCM (2×500 mL, then 250 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to 1.2 L. To this solution was added water (305 mL), NaHCO3 (136 g) and I2 (90.7 g). The reaction mixture was stirred at 25 C. for 40 h and diluted with 8% aqueous NaHCO3 (750 mL), water (750 mL) and DCM (300 mL). Following phase separation, the combined organic layer was extracted water (1 L). The combined aqueous layers were then washed with isopropyl acetate (300 mL), cooled to 0 C. and acidified by the addition of 2 N aqueous HCl (1.1 L). The aqueous phase was extracted with DCM (3×1 L), and the combined organic layer was washed with 10% aqueous NaHSO3 (2 L) and 10% aqueous NaCl (1.5 L). The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The resulting solid was twice dissolved and re-concentrated from isopropyl acetate (1 L). Additional isopropyl acetate (100 mL) was charged to the solid, the solution was heated to 50 C. and n-heptane (800 mL) was added. After cooling to 20 C. over 4 h, the slurry was cooled to 5 C. aged for 2 h. The product was collected by filtration, washed with n-heptane (2×150 mL) and dried to afford compound 4 as a light yellow solid (66.5 g, 74% yield from compound 2). 1H NMR (400 MHz, d6-DMSO, delta): 12.5 (s, 1H) 4.23-4.17 (m, 1H), 3.32-3.16 (m, 2H), 2.28-2.22 (m, 1H), 1.74 (dd, J=12.7, 4.3 Hz, 0.6H rotamer 1), 1.67 (dd, J=12.7, 3.7 Hz, 0.4H rotamer 2), 1.39 (s, 4H rotamer 1), 1.35 (s, 5H rotamer 2), 0.59-0.45 (m, 4H). 13C NMR (100 MHz, d6-DMSO, delta): 173.9, 173.5, 153.4, 153.0, 78.7, 78.6, 59.1, 58.8, 53.7, 53.4, 38.2, 37.5, 28.1, 27.9, 20.5, 19.9, 12.2, 11.5, 8.8, 8.3.

Reference： [1]Patent: US2013/324740,2013,A1 .Location in patent: Paragraph 0131; 0132; 0133; 0135; 0136; 0137

48
[ 593-71-5 ]
[ 6919-61-5 ]
[ 29179-20-2 ]
[ 1630982-22-7 ]
[ 532-27-4 ]

Reference： [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 1761 - 1766

49
[ 325486-45-1 ]
[ 593-71-5 ]
[ 1630982-34-1 ]

Reference： [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 1761 - 1766

50
[ 593-71-5 ]
[ 4674-50-4 ]
[ 1630982-36-3 ]

Reference： [1]Advanced Synthesis and Catalysis,2014,vol. 356,p. 1761 - 1766

51
[ 3913-81-3 ]
[ 593-71-5 ]
(E)-1-chloro-3-undecen-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium In tetrahydrofuran; diethyl ether at -100℃; for 0.366667h; Inert atmosphere;	General Procedure A for the Preparation of Vinyl Oxirane Substrates General procedure: To a 50 mL round bottom flask equipped with a magnetic stir bar, sequentially wasintroduced THF (5 mL), Et2O (5 mL), the corresponding enone (197 mg, 1.23 mmol, 1.0eq) and chloroiodomethane (0.13 mL, 1.84 mmol, 1.5 eq). The reaction mixture wascooled to -100 °C (isopropanol / liquid nitrogen bath) for 10 min. nBuLi (1.6 M, 1.15 mL,1.94 mmol, 1.5 eq) was added dropwise via a syringe (c.a. 2 min), and the reactiontemperature was maintained at -100 °C for 20 min and quenched with saturated NH4Cl (2mL). The product was extracted with EtOAc (3 x 5 mL), and the organic layers werecombined, washed with DI water (2 mL) and brine (2 mL). The organics were collected,dried with anhydrous MgSO4, filtered and concentrated in vacuo. In most cases, thealcohol intermediates were pure enough and were used in the next step without furtherpurification.To a 10 mL round bottom flask equipped with a magnetic stir bar, sodium hydride (60%in mineral oil, 34 mg, 0.84 mmol, 2.0 eq) and freshly distilled DMSO (1 mL) were addedand the slurry was stirred at room temperature. The allylic alcohol (90 mg, 0.42 mmol,1.0 eq) in freshly distilled DMSO (2.0 mL) was added dropwise (c.a. 2 min), and thereaction was stirred at room temperature until all of the allylic alcohol was consumed(TLC, 2 to 4 hours on average). The reaction was carefully quenched by slow addition ofsaturated NaHCO3 (1mL). The vinyl oxirane was extracted with Et2O (4 x 5 mL), and the organic layers were combined, washed with DI water (4 x 1 mL) and brine (1 mL). Theorganics were collected, dried with anhydrous MgSO4, filtered and concentrated in vacuo.The crude vinyl oxirane was purified by flash column chromatography. Note: It isessential to saturate the silica gel with triethylamine (TEA) prior to use as many of thevinyl oxiranes are sensitive to acid.

Reference： [1]Guo, Boying; Vitaku, Edon; Njardarson, Jon T. [Tetrahedron Letters, 2014, vol. 55, # 21, p. 3232 - 3234]

52
[ 593-71-5 ]
1-phenylethylisocyanate [ No CAS ]
[ 13230-80-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With methyllithium; lithium bromide; In diethyl ether; at -78℃; for 1.0h;	General procedure: To a cooled (-78C) solution of isocyanate (1.0 equiv) in dry Et2O (1 M concentration) was added the dihalomethane derivative (1.5 equiv). After 2 min, an ethereal solution of 1.5 M MeLi-LiBr (1.25equiv) was added dropwise over 5 min. The resulting solution was stirred for the appropriate time (see Table 1 and Scheme 2) at that temperature. Sat. aq NH4Cl was added (2 mL/mmol substrate) and the cooling bath was removed, the mixture was stirred till it reached r.t., and then it was extracted with additional Et2O (2 × 5 mL) and washed with water (5 mL) and brine (10 mL). The organic phase was dried (anhyd Na2SO4), filtered, and the solvent removed under reduced pressure to give pure samples of haloacetamides.

Reference： [1]Synthesis,2014,vol. 46,p. 2897 - 2909
[2]Advanced Synthesis and Catalysis,2015,vol. 357,p. 21 - 27

53
[ 50651-75-7 ]
[ 593-71-5 ]
[ 258516-84-6 ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; for 1h;Reflux;	In one embodiment, the present invention can include a method of preparing the POM reagent dibenzyl(choloromethyl)phosphate, as shown in reaction Scheme 5 of FIG. 5. Briefly, CH2ClI (5 mL; 68.6 mmol) is reacted with silver dibenzyl phosphate (2 g, 52 mmol) in about 25 mL toluene and refluxed for about 1 hour before the solvent is removed and processed through a separation column with 1/1EA/H in order to produce dibenzyl(choloromethyl)phosphate as confirmed via TLC.
	In toluene; for 1h;Reflux;	[0101] In one embodiment, the present invention can include a method of preparing the POM reagent dibenzyl(choloromethyl)phosphate, as shown in reaction Scheme 5 of Figure 5. Briefly, CH2CII (5 mL; 68.6 mmol) is reacted with silver dibenzyl phosphate (2 g, 52 mmol) in about 25 mL toluene and refluxed for about 1 hour before the solvent is removed and processed through a separation column with 1/lEA/H in order to producedibenzyl(choloromethyl)phosphate as confirmed via TLC.

Reference： [1]Patent: US2015/111858,2015,A1 .Location in patent: Paragraph 0069
[2]Patent: WO2016/77346,2016,A1 .Location in patent: Paragraph 0101

54
[ 593-71-5 ]
[ 24210-19-3 ]
[ 90105-41-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: Chloroiodomethane; methyl (2S)-3-methyl-[(benzyloxy)carbonylamino]butanoate With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2.5h; Inert atmosphere; Stage #2: With acetic acid In tetrahydrofuran at -70 - 20℃;	38.3 Step 3 Step 3. To the solution of compound 38-3 (10 g, 37.7 mmol) in THF (20 mL) was added C1CH2I (26.6 g, 151 mmol). After it was cooled to -78°C, LDA was added slowly in 2 h. After it was stirred at -78°C for 30 min under N2, HO Ac (21 mL, 377 mmol) in THF was added under -70°C. It was warmed to r.t, and EtOAc (30 mL) was added and the mixture was poured to brine. It was extracted with EtOAc (80 mL x 3), dried over Na2S04, concentrated, and purified by column chromatography on silica gel (PE: EtOAc= 5: 1) to give compound 38-4.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2015/95227, 2015, A2 Location in patent: Page/Page column 130; 131

55
[ 41042-12-0 ]
[ 593-71-5 ]
1-n-propylspiro[indole-3,2'-oxiran]-2(1H)-one [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 172 - 177

56
[ 875003-43-3 ]
[ 593-71-5 ]
7-fluoro-1-methylspiro[indole-3,2'-oxiran]-2(1H)-one [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2016,vol. 358,p. 172 - 177

57
[ 4630-82-4 ]
[ 593-71-5 ]
[ 57539-95-4 ]

Reference： [1]Organic Letters,2016,vol. 18,p. 2040 - 2043

58
[ 647857-39-4 ]
[ 593-71-5 ]
[ 1052686-67-5 ]
[ 1360944-30-4 ]
1-(5-bromo-1H-indazol-3-yl)ethan-1-one [ No CAS ]
[ 76-05-1 ]
(2R,4S)-2-(2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)acetyl)-N-(6-bromopyridin-2-yl)-4-fluoropyrrolidine-1-carboxamide [ No CAS ]
(2S,4S)-2-(2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)acetyl)-N-(6-bromopyridin-2-yl)-4-fluoropyrrolidine-1-carboxamide [ No CAS ]

Reference： [1]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 1171; 1172; 1173

59
[ 647857-39-4 ]
[ 593-71-5 ]
[ 1052686-67-5 ]
1-(5-bromo-1H-indazol-3-yl)ethan-1-one [ No CAS ]
tert-butyl (2R,4S)-2-(2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)acetyl)-4-fluoropyrrolidine-1-carboxylate [ No CAS ]
tert-butyl (2S,4S)-2-(2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)acetyl)-4-fluoropyrrolidine-1-carboxylate [ No CAS ]

Reference： [1]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 1169

60
[ 647857-39-4 ]
[ 593-71-5 ]
[ 1052686-67-5 ]
1-(5-bromo-1H-indazol-3-yl)ethan-1-one [ No CAS ]
[ 76-05-1 ]
2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)-1-((2R,4S)-4-fluoropyrrolidin-2-yl)ethan-1-one trifluoroacetate [ No CAS ]
2-(3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl)-1-((2S,4S)-4-fluoropyrrolidin-2-yl)ethan-1-one trifluoroacetate [ No CAS ]

Reference： [1]Patent: WO2017/35353,2017,A1 .Location in patent: Paragraph 1170

61
[ 593-71-5 ]
17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17β-carboxylic ethoxycarboxylic anhydride [ No CAS ]
[ 82034-46-6 ]

Yield	Reaction Conditions	Operation in experiment
89%		To 50L reactor, add 1.9 kg intermediate 4, hexamethylphosphoric acid triamide 19L, sodium ethoxide 0.26 kg. React under the condition of room temperature for 24 hours. Add chloroiodomethane 1.4 kg. Stir for 2 hours. The reaction liquid quickly add 570L in water, separate out a large amount of yellow solid, filtering. The filter cake is added to the chloroform 5.7L dissolved, for sequentially 0.3M sodium thiosulfate solution 1.9L, 0 . 4M sodium bicarbonate solution, 1.9L saturated salt water 1.9L washing liquid, anhydrous sodium sulfate drying, decolorized with active carbon. Filtered, concentrated under reduced pressure to dryness; anhydrous ethanol is added 13.3L, heating to reflux, the solid is completely dissolved, gradually cooling crystallization, filtration. 40 C blast drying, to obtain white solid 1.6 kg, yield 89%.

Reference： [1]Patent: CN106554383,2017,A .Location in patent: Paragraph 0025; 0031; 0032

62
[ 593-71-5 ]
[ 6919-61-5 ]
[ 18156-74-6 ]
2-chloro-N-methoxy-N-methyl-1-phenyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

63
[ 593-71-5 ]
[ 6919-61-5 ]
[ 18156-74-6 ]
2-chloro2-iodo-N-methoxy-N-methyl-1-phenyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

64
[ 593-71-5 ]
[ 6919-61-5 ]
[ 18156-74-6 ]
2-chloro-N-methoxy-N-methyl-1-phenyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]
[ 532-27-4 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

65
[ 75-77-4 ]
[ 593-71-5 ]
[ 6919-61-5 ]
2-chloro-N-methoxy-N-methyl-1-phenyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]
[ 532-27-4 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

66
[ 17906-35-3 ]
[ 593-71-5 ]
[ 6919-61-5 ]
[ 532-27-4 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

67
[ 593-71-5 ]
[ 6919-61-5 ]
[ 69739-34-0 ]
[ 532-27-4 ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

68
[ 593-71-5 ]
[ 116332-61-7 ]
[ 18156-74-6 ]
2-chloro-N-methoxy-N-methyl-1-[4-(trifluoromethyl)phenyl]-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: Chloroiodomethane; N-methoxy-N-methyl-4-trifluoromethylbenzamide In tetrahydrofuran at -78℃; for 0.0333333h; Inert atmosphere; Stage #2: With methyllithium lithium bromide In tetrahydrofuran; diethyl ether at -78℃; for 0.75h; Inert atmosphere; Stage #3: 1-(Trimethylsilyl)imidazole Further stages;

Reference： [1]Castoldi, Laura; Holzer, Wolfgang; Langer, Thierry; Pace, Vittorio [Chemical Communications, 2017, vol. 53, # 68, p. 9498 - 9501]

69
[ 226260-01-1 ]
[ 593-71-5 ]
[ 18156-74-6 ]
2-chloro-1-(3-fluorophenyl)-N-methoxy-N-methyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

70
[ 198967-24-7 ]
[ 593-71-5 ]
[ 18156-74-6 ]
2-chloro-1-(2-fluorophenyl)-N-methoxy-N-methyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

71
[ 593-71-5 ]
[ 95091-92-2 ]
[ 18156-74-6 ]
2-chloro-1-(2-furyl)-N-methoxy-N-methyl-1-[(trimethylsilyl)oxy]ethanamine [ No CAS ]

Reference： [1]Chemical Communications,2017,vol. 53,p. 9498 - 9501

72
[ 593-71-5 ]
[ 917-54-4 ]
[ 4674-50-4 ]
(4R,4aS,6R)-6-isopropenyl-2,4,4atrimethyl-2,3,4,4a,5,6,7,8-octahydro-2-naphthalenecarbaldehyde [ No CAS ]
(4R,4aS,6R)-6-isopropenyl-2,4,4a-trimethyl-2,3,4,4a,5,6,7,8-octahydro-2-naphthalenecarbaldehyde [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 12677 - 12682
Angew. Chem.,2017,vol. 129,p. 12851 - 12856,6

73
[ 593-71-5 ]
[ 100-39-0 ]
[ 4674-50-4 ]
(2S,4R,4aS,6R)-2-benzyl-6-isopropenyl-4,4a-dimethyl-2,3,4,4a,5,6,7,8-octahydro-2-naphthalenecarbaldehyde [ No CAS ]
(4R,4aS,6R)-2-benzyl-6-isopropenyl-4,4a-dimethyl-2,3,4,4a,5,6,7,8-octahydro-2-naphthalenecarbaldehyde [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 12677 - 12682
Angew. Chem.,2017,vol. 129,p. 12851 - 12856,6

74
[ 930-30-3 ]
[ 593-71-5 ]
[ 83902-02-7 ]
1-(2,6-dimethylbenzyl)-2-cyclopentene-1-carbaldehyde [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 12677 - 12682
Angew. Chem.,2017,vol. 129,p. 12851 - 12856,6

75
[ 593-71-5 ]
[ 1626-24-0 ]
[ 27259-63-8 ]

Reference： [1]Chemical Communications,2018,vol. 54,p. 10112 - 10115

76
[ 593-71-5 ]
[ 180609-56-7 ]
benzyl 2-(2-chloroacetyl)-1-piperidinecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		To a cooled solution (-78C) of 0.42 g (2.2 eq.) chloro-iodo-methane in 10 mL THF, 1.58 mL (2.2 eq.) of LDA 1.5 M solution in THF was added dropwise in a nitrogen atmosphere. The temperature was maintained below -72C. After stirring for additional 10 min at -78 C a solution of 0.3 g (1 eq.) of 1- benzyl 2-methyl 1,2-piperidinedicarboxylate in 3 mL THF was added dropwise. The internal temperature was maintained not higher than -72 C. After stirring for additional 5 min 1.08 mL (1.5 eq.) of LDA 1.5 M solution in THF was added dropwise. The internal temperature was maintained below - 72C. After stirring for further 30 min at -78C the reaction mixture was quenched with a solution of 1.2 g acetic acid in lOmL THF. The reaction mixture was allowed to warm to ambient temperature and 20 mL of water was added. The organic and aqueous phases were separated and the aqueous phase 3 times extracted with 25 mL of ethyl acetate. The combined organic washings were dried over magnesium sulphate, filtered, the solvents evaporated in vacuum and flashed chromatographed using heptane/dioxane 4: 1 mixture to give 0.15 g of the title product as almost colorless oil (Rf 0.12, yield 47%).

Reference： [1]Patent: WO2019/86469,2019,A1 .Location in patent: Page/Page column 33; 34

77
[ 593-71-5 ]
[ 144701-48-4 ]
C₆₇H₆₀N₈O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With sodium carbonate; In dimethyl sulfoxide; at 65℃; for 8h;	1.0 g of telmisartan was added to 20 mL of dimethyl sulfoxide, 0.67 g of sodium carbonate and 1.07 g of chloroiodomethane were added, and the mixture was heated to 65 C for 8 hours, followed by filtration to remove insoluble matter, and the filtrate was frozen. The dryer was lyophilized, and the obtained residue was subjected to column chromatography [HP-Silica normal phase silica gel, eluent was n-hexane: ethyl acetate = (12:1, V/V)] to separate the target product. The telmisartan methylene dimer was obtained in an amount of 1.82 g, and the HPLC purity was 99.2%, and the yield was 90%.

Reference： [1]Patent: CN109928932,2019,A .Location in patent: Paragraph 0050; 0051

78
[ 593-71-5 ]
[ 632-85-9 ]
C₁₈H₁₈O₁₃P₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.31 g		2 g of <strong>[632-85-9]wogonin</strong>, dissolved in 20 ml of tetrahydrofuran, Add 20 ml of chloroiodomethane at 30 C. Stir the reaction for 16 hours, Evaporated at 60 C under reduced pressure. Add 20 ml of acetonitrile to dissolve the residue as an intermediate. Another 9 ml of triethylamine was dissolved in 10 ml of acetonitrile. Add 3.6ml of phosphoric acid, After the drop is over, Slowly drip into the intermediate with stirring. Continue to stir the reaction at 60 C for 12 hours. Evaporate the solvent, The residue was dissolved in 20 ml of water. Add 10 ml × 3 wash water layers of ethyl acetate. Water layer filtration clarification, Lyophilization gave Compound B 0.31 g.

Reference： [1]Patent: CN102516301,2016,B .Location in patent: Paragraph 0031; 0032

79
[ 593-71-5 ]
4-chloroquinoline-6,7-diol [ No CAS ]
[ 59134-89-3 ]

Yield	Reaction Conditions	Operation in experiment
28.6%	With caesium carbonate In N,N-dimethyl-formamide at 110℃;	40.1 Step 1: Synthesis of 8-chloro- [1,3] dioxolene [4,5-g] quinoline 4-chloroquinoline-6,7-diol (2.67g, 13.0mmol, 1.0eq) was dissolved in DMF (10mL), and cesium carbonate (6.67g, 20.0mmol, 1.5eq) and chloroiodomethane (3.61g) were added. , 20.0 mmol, 1.5 eq), and reacted at 110 ° C overnight.The reaction was monitored for completeness by TLC, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (dichloromethane: methanol = 100: 1) to obtain the product (746.6 mg, yield: 28.6%).

Reference： [1]Current Patent Assignee: NANJING TRANSTHERA BIOSCIENCES - CN110041316, 2019, A Location in patent: Paragraph 0866; 0870-0872

80
[ 611-97-2 ]
[ 593-71-5 ]
2-chloro-2,2-bis-(p-tolyl)acetaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: Chloroiodomethane With lithium diisopropyl amide In tetrahydrofuran; n-heptane; ethylbenzene at -20℃; Flow reactor; Stage #2: bis(p-methylphenyl)-methanone In tetrahydrofuran; n-heptane; ethylbenzene at -20℃; Flow reactor; chemoselective reaction;

Reference： [1]Colella, Marco; Degennaro, Leonardo; Luisi, Renzo; Musci, Pantaleo; Romanazzi, Giuseppe; Sivo, Alessandra [Organic Letters, 2020, vol. 22, # 9, p. 3623 - 3627]

81
[ 593-71-5 ]
[ 91419-53-3 ]
tert-butyl 3-(chloromethyl)-3-cyanopiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: (+/-)-2-N-tert-butoxycabonylpiperidine-3-carbonitrile With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: Chloroiodomethane In tetrahydrofuran at -78 - 20℃; for 15h; Inert atmosphere;

Reference： [1]Blahun, Oleksandr P.; Melnychenko, Heorhii; Kuchkovska, Yuliya O.; Zhersh, Serhii; Tolmachev, Andrey A.; Grygorenko, Oleksandr O. [European Journal of Organic Chemistry, 2020, vol. 2020, # 22, p. 3261 - 3269]

82
[ 593-71-5 ]
[ 5438-19-7 ]
chloromethyl 4-propoxybenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46.63%	With triethylamine In N,N-dimethyl-formamide at 20℃; for 5h;

Reference： [1]Li, Zhonglin; Lin, Hao; Zhou, Junwen; Chen, Liangzhu; Pan, Zhikun; Fang, Binghu [Drug Development Research, 2021, vol. 82, # 2, p. 198 - 206]

83
[ 593-71-5 ]
[ 94651-33-9 ]
1-(2-chloroethyl)-2-(trifluoromethoxy)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: Chloroiodomethane; 2-(trifluoromethoxy)benzaldehyde With methyllithium lithium bromide In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: With hexylsilane; tris(pentafluorophenyl)borate In dichloromethane at 20℃; for 1h; Inert atmosphere; chemoselective reaction;

Reference： [1]Citarella, Andrea; Holzer, Wolfgang; Ielo, Laura; Langer, Thierry; Miele, Margherita; Pace, Vittorio; Urban, Ernst; Zehl, Martin [Organic Letters, 2020, vol. 22, # 19, p. 7629 - 7634]

84
[ 593-71-5 ]
[ 712-50-5 ]
(2-chloro-1-cyclohexylethyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: Chloroiodomethane; Cyclohexyl phenyl ketone With methyllithium lithium bromide In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: With hexylsilane; tris(pentafluorophenyl)borate In dichloromethane at 20℃; for 1h; Inert atmosphere; chemoselective reaction;

85
[ 593-71-5 ]
[ 342-24-5 ]
1-(2-chloro-1-phenylethyl)-2-fluorobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: Chloroiodomethane; o-fluorobenzophenone With methyllithium lithium bromide In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: With hexylsilane; tris(pentafluorophenyl)borate In dichloromethane at 20℃; for 1h; Inert atmosphere; chemoselective reaction;

86
[ 593-71-5 ]
[ 21221-93-2 ]
1-(2-chloro-1-phenylethyl)-3,5-bis(trifluoromethyl)benzene [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 7629 - 7634

87
[ 1212-08-4 ]
[ 593-71-5 ]
[ 24966-39-0 ]
1,3-dichloro-2-[(phenylsulfanyl)methyl]sulfanyl}benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: S-Phenyl benzenethiosulfonate; Chloroiodomethane In tetrahydrofuran at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: With methyllithium lithium bromide In tetrahydrofuran; diethyl ether for 1h; Inert atmosphere; Stage #3: 2,6-dichlorothiophenol With sodium iodide In tetrahydrofuran; diethyl ether; N,N-dimethyl-formamide at 0 - 20℃; for 6h; Inert atmosphere; chemoselective reaction;

Reference： [1]Ielo, Laura; Pillari, Veronica; Gajic, Natalie; Holzer, Wolfgang; Pace, Vittorio [Chemical Communications, 2020, vol. 56, # 82, p. 12395 - 12398]

88
[ 2949-92-0 ]
[ 593-71-5 ]
[ 24966-39-0 ]
1,3-dichloro-2-[(methylsulfanyl)methyl]sulfanyl}benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: methanethiosulfonic acid S-methyl ester; Chloroiodomethane In tetrahydrofuran at -78℃; for 0.0833333h; Inert atmosphere; Stage #2: With methyllithium lithium bromide In tetrahydrofuran; diethyl ether for 1h; Inert atmosphere; Stage #3: 2,6-dichlorothiophenol With sodium iodide In tetrahydrofuran; diethyl ether; N,N-dimethyl-formamide at 0 - 20℃; for 6h; Inert atmosphere; chemoselective reaction;

Reference： [1]Ielo, Laura; Pillari, Veronica; Gajic, Natalie; Holzer, Wolfgang; Pace, Vittorio [Chemical Communications, 2020, vol. 56, # 82, p. 12395 - 12398]

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Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
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

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 593-71-5 ] {[proInfo.proName]}

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Application In Synthesis of [ 593-71-5 ]

[ 593-71-5 ] Synthesis Path-Upstream 1~11

[ 593-71-5 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

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Disposal

Physical hazards

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