Name: 2181-42-2|Trimethylsulfonium iodide|98%
Brand: Ambeed
SKU: A261511
Price: 6.0 USD
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1
[ 2181-42-2 ]
[ 1143-50-6 ]
[ 24391-59-1 ]

Reference： [1]Canadian Journal of Chemistry,1969,vol. 47,p. 4327 - 4333

2
[ 4903-09-7 ]
[ 2181-42-2 ]
2-(3-chloro-4-methoxyphenyl)oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium hydroxide; In dimethyl sulfoxide; at 40℃; for 7h;Inert atmosphere;	To a mixture of <strong>[4903-09-7]3-chloro-4-methoxybenzaldehyde</strong> (2.00 g,11.7 mmol) and trimethylsulfonium iodide (3.35 g, 16.4 mmol) inDMSO (12 mL) was added potassium hydroxide (0.920 g,16.4 mmol). After stirring at 40 C for 7 h, the reaction mixturewas diluted with EtOAc (50 mL) and washed with H2O (100 mL).The aqueous layer was extracted with EtOAc (50 mL). To the combinedorganic layer was added toluene (100 mL), and the wholewas washed with H2O (100 mL), dried over Na2SO4, filtered andconcentrated in vacuo to give 2.25 g (quant.) of the title compoundas a pale yellow oil. The obtained compound 12a was used in thenext reaction without further purification. 1H NMR (300 MHz,CDCl3) d: 2.77 (1H, dd, J = 5.3, 2.6 Hz), 3.13 (1H, dd, J = 5.3,4.0 Hz), 3.80 (1H, dd, J = 4.0, 2.6 Hz), 3.90 (3H, s), 6.90 (1H, d,J = 8.4 Hz), 7.16 (1H, dd, J = 8.5, 2.1 Hz), 7.28 (1H, d, J = 2.2 Hz).

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 293 - 304
[2]Journal of Medicinal Chemistry,1982,vol. 25,p. 352 - 358

3
[ 84-51-5 ]
[ 2181-42-2 ]
C₁₈H₁₆O₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1982,vol. 25,p. 505 - 518

4
[ 13726-16-4 ]
[ 2181-42-2 ]
2-(4-Chloro-3-methoxy-phenyl)-oxirane [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1982,vol. 25,p. 352 - 358

5
[ 27752-24-5 ]
[ 2181-42-2 ]
[ 118676-15-6 ]
[ 118584-25-1 ]
[ 118584-25-1 ]

Reference： [1]Tetrahedron,1988,vol. 44,p. 81 - 90

6
[ 858-98-0 ]
[ 2181-42-2 ]
[ 68687-35-4 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium tert-butylate; In Isopropyl acetate; N,N-dimethyl-formamide; at 0 - 20℃; for 0.916667h;	SMe3I (0.63g, 3.09mmol) and KOtBu (0.47g, 4.24mmol) were added to a solution of 1 (0.69g, 1.91mmol) in dry DMF (16mL) under Ar. The reaction was stirred at 0C for 10min and then at room temperature for 45min. After this time, cold water was added and the product was extracted with diethyl ether. The organic phase was washed with brine (3×20mL), dried over anhydrous MgSO4, filtered and concentrated to dryness. Column chromatography (19:1 hexane-EtOAc) gave 24 compound 12 as white crystals (0.68g, 95%); mp 154-156C (lit. 155-157C) [54]. [alpha]25D [alpha]D25 +45 (c 0.4, CHCl3). IR (cm-1): 3027 (C-H aromatic), 2919-2862 (C-H aliphatic), 1602-1495 (C=C), 1233-1016 (C-O). 1H NMR (500MHz, CDCl3) delta 7.45 (m, 2H, Ar-Ho), 7.40 (m, 2H, Ar-Hm), 7.34 (m, 1H, Ar-Hp), 7.21 (d, 1H, J1,2=8.5Hz, H-1), 6.80 (dd, 1H, J2,1=8.5Hz, J2,4=2.7Hz, H-2), 6.75 (d, 1H, J4,2=2.7Hz, H-4), 5.05 (s, 2H, CH2-Ph), 2.98 (d, 1H, Jgem=5.1Hz, CH2a oxirane), 2.90 (m, 2H, H-6), 2.66 (d, 1H, Jgem=5.1Hz, CH2b oxirane), 2.32 (m, 1H, H-11a), 2.24 (m, 1H, H-9), 2.06 (m, 1H, H-16a), 1.96 (m, 1H, H-7a), 1.87 (m, 1H, H-16b), 1.86 (m, 1H, H-15a), 1.55 (m, 1H, H-12a), 1.53 (m, 1H, H-8), 1.53 (m, 1H, H-15b), 1.52 (m, 1H, H-14), 1.50 (m, 1H, H-11b), 1.40 (m, 1H, H-7b), 1.28 (m, 1H, H-12b), 0.94 (s, 3H, H-18). 13C NMR (125.7MHz, CDCl3) delta 156.9 (C-3), 138.1 (C-5), 137.4 (Ar-Cipso), 132.8 (C-10), 128.7 (x2) (Ar-Cm), 128.0 (Ar-Cp), 127.6 (x2) (Ar-Co), 126.4 (C-1), 114.9 (C-4), 112.4 (C-2), 70.7 (C-17), 70.0 (CH2-Ph), 53.8 (CH2 oxirane), 51.9 (C-14), 44.0 (C-9), 40.5 (C-13), 39.0 (C-8), 34.0 (C-12), 29.9 (C-6), 29.2 (C-16), 27.3 (C-7), 26.1 (C-11), 23.4 (C-15), 14.4 (C-18). HRESI-MS calcd for C26H31O2 ([M+H]+): 375.2319, found: 375.2311.

Reference： [1]Organic Letters,2011,vol. 13,p. 4786 - 4789
[2]European Journal of Medicinal Chemistry,2018,vol. 143,p. 21 - 32
[3]Journal of Organic Chemistry,1981,vol. 46,p. 3259 - 3262
[4]Bioorganic and medicinal chemistry,2020

7
[ 2181-42-2 ]
[ 84-65-1 ]
[ 56588-78-4 ]

Yield	Reaction Conditions	Operation in experiment
80%		Preparation of trans-dispiro[oxirane-2,9'[10'H]-anthracene-10',2"-oxirane]7 To a two-necked flask NaH (13 mmol, 0.52 g, 60% in oil) was added under argon atmosphere and washed with n-hexane (3 * 20 mL). Then trimethylsolfunium iodide (12.64 mmol, 2.58 g) in dry DMSO (30 mL) was added slowly in darkness. The mixture was stirred for 8 h at rt. After that, anthraquinone (5.62 mmol, 1.17 g) in dry DMSO (30 mL) was added and stirred for 16 h at rt. After completion of the reaction, flask was put onto an ice bath; crushed ice (100 g) was added to the mixture and stirred for 30 min at 0 C. The white or yellow precipitate was filtered off, washed with water and dried. Yield 80%. m. p. 117-120 C, colorless solid, IR (KBr, nu/cm-1): 3040, 2980, 1479, 1450, 1318, 916, 896, 840, 762, 740. 1H NMR (400 MHz, CDCl3, ppm): delta 3.27 (s, 4H, CH2), 7.29-7.44 (m, 8H, Hb, Hc). 13C NMR (100 MHz, CDCl3, ppm): delta 54.5, 63.8, 122.3, 128.4, 135.4.

Reference： [1]Chemical Communications,1997,p. 1419 - 1420
[2]Journal of Molecular Structure,2015,vol. 1081,p. 248 - 253
[3]Journal of Medicinal Chemistry,1982,vol. 25,p. 505 - 518
[4]Journal of Fluorescence,2019,vol. 29,p. 933 - 943

8
[ 2181-42-2 ]
[ 961-07-9 ]
[ 578-76-7 ]
[ 107149-64-4 ]
[ 72398-32-4 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[2]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[3]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792

9
[ 2181-42-2 ]
[ 82-46-2 ]
[ 75905-56-5 ]

Reference： [1]Journal of Medicinal Chemistry,1982,vol. 25,p. 505 - 518

10
[ 2181-42-2 ]
[ 2140-79-6 ]
[ 91101-00-7 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[2]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792

11
[ 2181-42-2 ]
[ 123-11-5 ]
[ 6388-72-3 ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 20℃; for 20h;Cooling with ice; Inert atmosphere;	A solution of trimethylsulfonium iodide (2.58 g, 12.7 mmol) in DMSO (20 mL) was addeddropwise to an ice-cooled suspension of NaH (317 mg, 13.2 mmol, prepared from 529 mg60 % NaH in mineral oil) in THF (20 mL). To the ice-cooled mixture, a solution of4-methoxybenzaldehyde (1.50 g, 11.0 mmol) in THF (7 mL) was slowly added. The coolingbath was removed, the mixture was stirred at rt for 20 h and poured onto ice. The mixture was extracted with Et20 and the combined extracts were washed with water, brine, dried (Na2SO4) and concentrated to give the sub-title compound (1.61g, 10.7 mmol, 97 %)which was used in the next step without any further purification.
97%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 20℃; for 20h;Cooling with ice;	A solution of trimethylsulfonium iodide (2.58 g, 12.7 mmol) in DMSO (20 mL) was addeddropwise to an ice-cooled suspension of NaH (317 mg, 13.2 mmol, prepared from 529 mg60 % NaH in mineral oil) in THF (20 mL). To the ice-cooled mixture, a solution of4-methoxybenzaldehyde (1.50 g, 11.0 mmol) in THF (7 mL) was slowly added. The coolingbath was removed, the mixture was stirred at rt for 20 h and poured onto ice. The mixture was extracted with Et20 and the combined extracts were washed with water, brine, dried (Na2SO4) and concentrated to give the sub-title compound (1.61g, 10.7 mmol, 97%) which was used in the next step without any further purification.
84%	With sodium hydride; In dimethyl sulfoxide; mineral oil;	XVIII.I Intermediate Products According to B) Synthesis Route IX Intermediate Product 56: 2-(4-Methoxy-phenyl)-oxirane (process step 30) A solution of trimethylsulfonium iodide (4.0 g, 19.8 mmol) in DMSO (40 ml) was added to sodium hydride (60% in mineral oil, 1.32 g, 33 mmol) in a dry 2 neck RB flask under a nitrogen atmosphere. The solution was stirred at room temperature for 30 minutes, before it was cooled to 0 C. and a solution of 4-methoxybenzaldehyde in DMSO (10 ml) was added dropwise. The mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with water and EtOAc and the organic phase was washed with water and brine, dried (Na2SO4) and concentrated in vacuo to give intermediate product 56 (2.1 g, 84%).

	In tetrahydrofuran; dimethyl sulfoxide; mineral oil;	EXAMPLE 7 A suspension of 4.84 g. of sodium hydride (57% mineral oil dispersion) in 70 ml. of dry dimethyl sulfoxide is heated at about 65 C. under argon with stirring for 1 hour. Dry tetrahydrofuran (75 ml.) is added and the resulting solution is cooled to -5 C. <strong>[2181-42-2]Trimethylsulfonium iodide</strong> (19 g., 92.8 mmol) is added very slowly and stirring is continued for about 5 minutes. A solution of 12.6 g. (92.8 mmol) of p-methoxybenzaldehyde in 120 ml. of tetrahydrofuran is added and the temperature is maintained at -5 C. After addition is completed the mixture is allowed to warm to room temperature, poured into water and extracted with ether. The extract is washed with saturated sodium chloride solution, dried and evaporated to give p-methoxystyrene oxide.
	In tetrahydrofuran; dimethyl sulfoxide; mineral oil;	EXAMPLE 9 A suspension of 4.84 g. of sodium hydride (57% mineral oil dispersion) in 70 ml. of dry dimethyl sulfoxide is heated at about 65 C. under argon with stirring for 1 hour. Dry tetrahydrofuran (75 ml.) is added and the resulting solution is cooled to -5 C. <strong>[2181-42-2]Trimethylsulfonium iodide</strong> (19 g., 92.8 mmole) is added very slowly and stirring is continued for about 5 minutes. A solution of 12.6 g. (92.8 mmole) of p-methoxybenzaldehyde in 120 ml. of tetrahydrofuran is added and the temperature is maintained at -5 C. After addition is completed the mixture is allowed to warm to room temperature, poured into water and extracted with ether. The extract is washed with saturated sodium chloride solution, dried and evaporated to give p-methoxystyrene oxide.

Reference： [1]Patent: WO2017/153737,2017,A1 .Location in patent: Page/Page column 45
[2]Patent: WO2019/53428,2019,A1 .Location in patent: Page/Page column 41; 42
[3]Synthetic Communications,1982,vol. 12,p. 613 - 620
[4]Synthetic Communications,1995,vol. 25,p. 2695 - 2702
[5]Patent: US2012/214798,2012,A1
[6]Organic and Biomolecular Chemistry,2018,vol. 16,p. 4833 - 4839
[7]European Journal of Organic Chemistry,2015,vol. 2015,p. 7009 - 7019
[8]Chemical Communications,2018,vol. 54,p. 11340 - 11343
[9]Journal of Organic Chemistry,2019,vol. 84,p. 4443 - 4450
[10]Organic and Biomolecular Chemistry,2008,vol. 6,p. 1339 - 1343
[11]Journal of Heterocyclic Chemistry,1985,vol. 22,p. 745 - 750
[12]Dalton Transactions,2015,vol. 44,p. 19464 - 19468
[13]Tetrahedron Letters,1982,vol. 23,p. 5283 - 5286
[14]Journal of Organic Chemistry,2004,vol. 69,p. 8504 - 8505
[15]Journal of Organic Chemistry,2006,vol. 71,p. 6829 - 6833
[16]Patent: US4011319,1977,A
[17]Angewandte Chemie - International Edition,2011,vol. 50,p. 6056 - 6059
[18]Dalton Transactions,2016,vol. 45,p. 14184 - 14190
[19]Chemical Communications,2017,vol. 53,p. 4308 - 4311
[20]Patent: US4108989,1978,A

12
[ 2181-42-2 ]
[ 2140-72-9 ]
[ 120057-51-4 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[2]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792

13
[ 2181-42-2 ]
[ 118-00-3 ]
[ 578-76-7 ]
[ 22164-16-5 ]
[ 39708-05-9 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[2]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792
[3]Journal of the Chemical Society. Perkin transactions I,1980,p. 2787 - 2792

14
[ 1794-45-2 ]
[ 2181-42-2 ]
[ 176723-06-1 ]

Reference： [1]Archiv der Pharmazie,1996,vol. 329,p. 125 - 132
[2]Chemical Communications,2020,vol. 56,p. 2131 - 2134

15
[ 32024-15-0 ]
[ 2181-42-2 ]
2-(3-Iodo-4,5-dimethoxy-phenyl)-oxirane [ No CAS ]

Reference： [1]South African Journal of Chemistry,1996,vol. 49,p. 40 - 46

16
[ 119-61-9 ]
[ 2181-42-2 ]
[ 882-59-7 ]

Yield	Reaction Conditions	Operation in experiment
36.6%		(1) Under an Ar atmosphere, 14.49 g of trimethylsulfonium iodide and 60 mL of dry dimethyl sulfoxide (DMSO) were charged, and then 2.63 g of NaH (60%) was dividedly added to the mixture at 20 C. to 30 C. The resultant mixture was stirred at the same temperature for 1.5 hours. Next, to the mixture, 10.0 g of benzophenone was dividedly added, and the resultant mixture was stirred at 45 C. to 52 C. for 1 hour. After confirming the disappearance of the starting materials by TLC, the reaction mixture was poured into 200 mL of ice water and 200 mL of EtOAc, and the resultant mixture was stirred for a while. After the standing and the liquid separation, the obtained organic layer was washed successively with 200 mL of a saturated NaHCO3 aqueous solution and 200 mL of saline solution, and then the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, to give concentrated residues (11.7 g). The obtained concentrated residues were purified by silica gel column chromatography (120 g of silica gel, Heptane/EtOAc=60/1 to 40/1 to 20/1), and then the column fractions containing the target object was concentrated under reduced pressure, to give 1,1-diphenylethylene oxide (3.94 g, yield 36.6%) as colorless oil.

Reference： [1]Journal of the American Chemical Society,2013,vol. 135,p. 6177 - 6183
[2]Synthetic Communications,2003,vol. 33,p. 2135 - 2143
[3]Letters in Organic Chemistry,2011,vol. 8,p. 509 - 514
[4]Patent: US2018/51018,2018,A1 .Location in patent: Paragraph 0234; 0235; 0236; 0237; 0238
[5]Journal of the Chemical Society. Perkin Transactions 2 (2001),1998,p. 1407 - 1411
[6]Chemical Communications,2017,vol. 53,p. 4308 - 4311
[7]Helvetica Chimica Acta,2019,vol. 102

17
[ 2181-42-2 ]
[ 874-42-0 ]
[ 13692-15-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	With potassium hydroxide; In water; acetonitrile; at 60℃; for 3h;Inert atmosphere;	To a stirred solution of trimethylsulfonium iodide (1.224 g, 6 mmol) in acetonitrile (3 mL) at room temperature was added potassium hydroxide (0.464 g, 9 mmol). Then 2,4-dichlorobenzaldehyde 1 (1.05 g, 6 mmol) dissolved in 3 mL of acetonitrile was slowly added, followed by 0.05 mL of distilled water. The solution was stirred for 3 h at 60 C under nitrogen atmosphere, after which time TLC (treated with 0.05 mL of triethylamine) indicated the disappearance of the starting material. Then the solution was brought to room temperature with continuous stirring for 15 min, and the solvent was evaporated under reduced pressure to give the yellow oil 2 (1.054 g, 93%). Rf: 0.62 (EtOAc/Hex 2/8). 1H NMR: (300 MHz, CDCl3) d 7.38 (d, J 1.8 Hz, 1H),7.26e7.16 (m, 2H), 4.17e4.14 (m, 1H, OeCH), 3.19 (dd, J 4.2, 5.6 Hz,1H, OeCH2), 2.65 (dd, J 1.5, 3.3 Hz, 1H, OeCH2) ppm. 13C NMR:(75.4 MHz, CDCl3) d 134.1 (CeCl), 133.9 (C), 133.6 (CeCl), 128.8(C), 127.3 (C), 126.5 (C), 50.6 (OeCH), 49.5 (OeCH2) ppm.

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 97,p. 275 - 279
[2]Organic Preparations and Procedures International,1992,vol. 24,p. 342 - 345
[3]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2691 - 2696

18
[ 2181-42-2 ]
[ 79099-07-3 ]
[ 147804-30-6 ]

Yield	Reaction Conditions	Operation in experiment
98%		To a solution of NaH (1.68 g, 42.0 mmol) in dry DMF (70 mL) at 0 C., (CH3)3SI (8.56 g, 42.0 mmol) was added and allowed to stirred at room temperature for 30 minutes. tert-Butyl 4-oxopiperidine-1-carboxylate (7.00 g, 35.0 mmol) was added at 0 C. and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was quenched with water (50.0 mL) and extracted with EtOAc (2*100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated under reduced pressure to give the product (7.40 g, 98%) as colorless oil. MS: m/z=214 (M+H+).
82%		A 60% suspension of NaH in oil (230 mg; 5.5 mmol) in DMSO (6 ml) under argon was treated with <strong>[2181-42-2]trimethylsulphonium iodide</strong> (1.26 g; 5.75 mmol) at 5C. The mixture was stirred for 30 minutes and C7 (l. Og; 5 mmol) was added. The mixture was stirred for 1 hour at room temperature. The mixture was partitioned between water and diethyl ether. The diethyl ether was evaporated and the residue purified by flash chromatography eluting with increasingly polar mixtures of EtOAc/CH2C12 (0-30% EtOAc) to give D7 (870 mg). Yield: 82%
70%		Step 1. Synthesis of Intermediate 7-2. To a solution of <strong>[2181-42-2]trimethylsulfoxonium iodide</strong> (26.5 g, 130 mmol) in 50 mL of DMSO at 10 C under N2, NaH (5.18 g, 60% in miniral oil, 130 mmol) was added portionwise and the mixture was stirred at 10 C for 30 mins. Intermediate 7-1 (20 g, 100 mmol) in DMSO (50 mL) was added dropwise maintaining the temperature below 15 C and stirring was continued at 15 C for 20 hrs. The reaction was quenched at 10 C with water (200 mL) and extracted with MTBE (2 x 300 mL). The combined organic phases were washed with water (2 x 400 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo to give a residue, which was purified by silica gel chromatography (PE:EtOAc = 6:1) to give Intermediate 7-2 (15 g, 70%) as an off-white solid. (0337) 1H NMR (400 MHz, CDCl3) delta 3.77-3.66 (m, 2H), 3.43 (m, 2H), 2.69 (s, 2H), 1.86-1.72 (m, 2H), 1.52-1.39 (m, 11H).

65%

NaH in mineral oil (10 g, 0.25 mol, 50 %) was added in portions with stirring under an atmosphere of Ar to DMSO (150 mL) over a period of 20 min. Then the mixture was heated on a water-bath to 75 0C and stirred about 20 min at room temperature until evolution of hydrogen ceased. The mixture was cooled to 25 0C, diluted by adding THF (15O mL), cooled to 5 0C and treated with a solution of trimethylsulfonium iodide (51 g, 0.25 mol) in DMSO (200 mL). Then compound 1 (40 g, 0.2 mol) was added to the mixture. The reaction was heated to 25 0C and stirred at this temperature for ~2 h. Then pH was adjusted to 8 with glacial acetic acid and the mixture was diluted by adding water (500 mL), ethylacetate (400 mL), hexane (20O mL) and dichloromethane (10O mL). The organic layer was separated, washed with water (2 x 200 mL), diluted by adding dichloromethane (100 mL) and washed with brine. Combined aqueous layer was extracted with ethylacetate (300 mL) and hexane (150 mL). The organic layer was washed similarly. Then organic layers were filtered sequentially through SiO2 (50 g). The combined filtrate was evaporated and the residue (45 g) was crystallized from hexane (60 ml_) at -18 0C to give the title compound as white crystals (bp 56-590C) in 65% (28 g, 0.13 mol) yield.

Reference： [1]Patent: US2017/217986,2017,A1 .Location in patent: Paragraph 0475; 0476
[2]Patent: WO2005/79805,2005,A1 .Location in patent: Page/Page column 72
[3]Patent: WO2017/173358,2017,A1 .Location in patent: Paragraph 00136
[4]Patent: WO2006/27694,2006,A1 .Location in patent: Page/Page column 67-68
[5]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3369 - 3374

19
[ 119-10-8 ]
[ 2181-42-2 ]
[ 142596-53-0 ]

Reference： [1]Synthetic Communications,2000,vol. 30,p. 4247 - 4254

20
[ 34036-07-2 ]
[ 2181-42-2 ]
[ 111991-13-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2691 - 2696

21
[ 74003-55-7 ]
[ 2181-42-2 ]
[ 390407-76-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 2691 - 2696

22
[ 14615-72-6 ]
[ 2181-42-2 ]
[ 50841-47-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2687 - 2692

23
[ 2181-42-2 ]
[ 2930-05-4 ]
[ 109613-59-4 ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10264 - 10266
[2]Journal of the American Chemical Society,2006,vol. 128,p. 1371 - 1378
[3]Organic Letters,2006,vol. 8,p. 5025 - 5028
[4]Organic Letters,2008,vol. 10,p. 2223 - 2226
[5]Journal of Organic Chemistry,2005,vol. 70,p. 5880 - 5889
[6]Organic Letters,2011,vol. 13,p. 5816 - 5819
[7]European Journal of Organic Chemistry,2012,p. 1025 - 1032
[8]Tetrahedron Asymmetry,2003,vol. 14,p. 1847 - 1856

24
[ 2181-42-2 ]
[ 129940-50-7 ]
[ 403985-96-6 ]

Yield	Reaction Conditions	Operation in experiment
54%		Stir trimethyisulfonium iodide (193.5 g, 948.2 mrnol) in THF (1264 mL) at ambient temperature for 75 minutes. Cool mixture to -50 C and add nbutyilithium (2.5 mol/L inexanes, 379 mL, 948,2 mmoi) via cannula, over a period of30 minutes. Allow the reaction to gradually warm to -30 C and stir fir 60 minutes. Add (2S)-2-?trityioxymethyi oxirane (100 g, 316.1 mmoi) portion wise, keeping the temperature below -10 C. After the complete addition , allow the reaction mixture to warm to room temperature and stir for 2 hours. Pour the reaction into saturated ammoniurn chloride, separate the phases, and extract the aqueous phase with ethylacetate. Combine the organic layers and dry over magnesium sulfate, Filter and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with methyl t-butyl ether: hexanes (10-15% gradient), to give the title compound (56.22 g, 54%). ES/MS miz 353 (M±Na).
54%		Scheme I, step A: Stir triniethylsulfonium iodide (193.5 g, 948.2 mmol) in THF (1264 mL) at ambient temperature for 75 minutes. Cool the mixture to -50 C and add nIC butyihthium (2.5 moi/L in hexanes, 379 mL, 948.2 mmoi) via cannula, over a period of30 minutes. Allow the reaction to gradually warm to -30 C and stir for 60 minutes. Add (2S)-2-trityloxyrnethyi oxirane (100 g, 316.1 rnmoi) portion wise, keeping the temperature below -10 C. After the complete addition, allow the reaction mixture to warm to room temperature and stir for 2 hours. Pour the reaction into saturatedammonium chloride, separate the phases, and extract the aqueous phase with ethyl acetate. Combine the organic layers and dry over magnesium sulfate. Filter and concentrate under reduced pressure to give a residue. Purif? the residue by silica gel chromatography, eluting with methyl t-butyi ether: hexanes (10-15% gradient), to give the title compound (56.22 g, 54%). ES/MS rn?z 353 (M-FNa).
54%		Stir trimethylsulfonium iodide (193.5 g, 948.2 mmol) in THF (1264 mL) at ambient temperature for 75 minutes. Cool mixture to -50 C and add n- butyllithium (2.5 mol/L in hexanes, 379 mL, 948.2 mmol) via cannula, over a period of 30 minutes. Allow the reaction to gradually warm to -30 C and stir for 60 minutes. Add (2S)-2-trityloxymethyl oxirane (100 g, 316.1 mmol) portion wise, keeping the temperature below -10 C. After the complete addition, allow the reaction mixture to warm to room temperature and stir for 2 hours. Pour the reaction into saturated ammonium chloride, separate the phases, and extract the aqueous phase with ethyl acetate. Combine the organic layers and dry over magnesium sulfate. Filter and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with methyl /-butyl ether: hexanes (10-15% gradient), to give the title compound (56.22 g, 54%). ES/MS m/z 353 (M+Na).

54%		Scheme 1, step A: Stir trimethylsulfonium iodide (193.5 g, 948.2 mmol) in THF (1264 mL) at ambient temperature for 75 minutes. Cool mixture to -50 C and add n- butyllithium (2.5 mol/L in hexanes, 379 mL, 948.2 mmol) via cannula, over a period of 30 minutes. Allow the reaction to gradually warm to -30 C and stir for 60 minutes. Add (2S)-2-trityloxymethyl oxirane (100 g, 316.1 mmol) portion wise, keeping the temperature below -10 C. After the complete addition, allow the reaction mixture to warm to room temperature and stir for 2 hours. Pour the reaction into saturated ammonium chloride, separate the phases, and extract the aqueous phase with ethyl acetate. Combine the organic layers and dry over magnesium sulfate. Filter and concentrate under reduced pressure to give a residue. Purify the residue by silica gel chromatography, eluting with methyl i-butyl ether: hexanes (10-15% gradient), to give the title compound (56.22 g, 54%). ES/MS m/z 353 (M+Na).
		25-(l) Synthesis of (S)-l-trityloxybut-3-en-2-olA solution of n-BuLi in hexane (2.6 M; 182 niL) was added dropwise to a solution of trimethylsulfonium iodide (96.8 g) in THF (800 niL) at -30C. After stirring at -20C for 20 min, (S)-trityl glycidyl ether (50.0 g) was added at the same temperature, and the mixture was stirred at RT for 30 min. Water was added to the reaction solution, followed by extraction with diethyl ether. The organic layer was dried over anhydrous MgSO4. The insoluble matter was separated by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (52.0 g). 1H-NMR (400 MHz, CDCl3) delta (ppm): 3.09-3.13 (m, IH), 3.20-3.23 (m, IH), 4.26-4.29 (m, IH), 5.14-5.32 (m, 2H), 5.76-5.84 (m, IH), 7.23-7.45 (m, 15H).

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 5880 - 5889
[2]Tetrahedron Asymmetry,2003,vol. 14,p. 1847 - 1856
[3]Patent: WO2016/176118,2016,A1 .Location in patent: Page/Page column 13; 19; 20
[4]Patent: WO2017/200863,2017,A1 .Location in patent: Page/Page column 17
[5]Patent: WO2018/34977,2018,A1 .Location in patent: Page/Page column 19; 22
[6]Patent: WO2018/75339,2018,A1 .Location in patent: Page/Page column 21; 24-25
[7]Patent: WO2011/9898,2011,A1 .Location in patent: Page/Page column 88

25
[ 51179-18-1 ]
[ 2181-42-2 ]
[ 484-29-7 ]
[ 827303-64-0 ]

Reference： [1]Tetrahedron Letters,2004,vol. 45,p. 9483 - 9485

26
[ 55676-21-6 ]
[ 2181-42-2 ]
[ 906744-23-8 ]

Reference： [1]Journal of Organic Chemistry,2006,vol. 71,p. 5538 - 5545

27
[ 2181-42-2 ]
[ 85960-55-0 ]
[ 117661-29-7 ]

Reference： [1]Synlett,2014,vol. 25,p. 501 - 504
[2]Angewandte Chemie - International Edition,2006,vol. 45,p. 5510 - 5515
[3]Synthesis,2011,p. 3343 - 3349

28
[ 2181-42-2 ]
[ 221103-69-1 ]
2-(3-ethynyl-thiophen-2-yl)-oxirane [ No CAS ]

Reference： [1]Heterocycles,2006,vol. 67,p. 233 - 246

29
[ 17408-14-9 ]
[ 2181-42-2 ]
2-methyl-2-(2-trifluoromethylphenyl)-oxirane [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2007,vol. 349,p. 1405 - 1417

30
[ 82386-89-8 ]
[ 2181-42-2 ]
[ 545410-66-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In water; acetonitrile; at 70℃; for 6h;	[0312] A. 2-Chloro-5-trifluoromethylphenylethylene oxide. To a stirred solution of 2-chloro-5-trifluoromethylbenzalhyde (2.05 g, 10 mmol) in acetonitrile (50 mL) at rt was added trimethylsulfonium iodide (2.04 g, 10 mmol) and 0.5 mL of water, followed by powdered KOH (1.05 g). The suspension was heated on an oil-bath at 70 C. under argon for 6 h. The reaction mixture was cooled, ether was added, and the suspension was filtered. The filtrate was concentrated and the residue purified by flash column chromatography (hexanes/EtOAc, 9:1) to give Compound A as a yellow oil (1.8 g).

Reference： [1]Patent: US2004/39033,2004,A1 .Location in patent: Page/Page column 42

31
[ 5381-20-4 ]
[ 2181-42-2 ]
[ 556025-68-4 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; methylamine; In methanol; water; acetonitrile;	(2) Preparation of 1-(3a,7a-dihydro-1-benzothien-3-yl)-2-(methylamino)ethanol. Potassium hydroxide (3.11 g) and H2O (0.12 mL) are added to acetonitrile (50 mL). Trimethylsulfonium iodide (5.65 g) and thianaphthene-3-carboxaldehyde (4.50 g) are then added. The reaction mixture is heated to 60 C. for 4 h. The reaction mixture is allowed to cool to room temperature and is then diluted with Et2O (25 mL). The precipitate is filtered off, and the filtrate is concentrated in vacuo. The resulting crude material is dissolved in methanol (40 mL) and added to a solution of methylamine in methanol (2M, 100 mL). The reaction mixture is stirred at room temperature for 3 d. The reaction mixture is concentrated in vacuo. The resulting brown oil is purified via column chromatography (CHCl3/methanol, 95/5, 90/10; CHCl3/methanol/NH4OH, 90/10/1) to yield 1.75 g of the title compound as a yellow solid. Physical characteristics: Mp 98-102 C.; 1H NMR (400 MHz, DMSO-d6) delta 7.98-7.90, 7.51, 7.60, 7.40-7.33, 5.43, 5.04, 2.80, 2.34; MS (ESI+) m/z 208 (M+H)+.

Reference： [1]Patent: US2003/207877,2003,A1

32
[ 394-25-2 ]
[ 2181-42-2 ]
[ 1239985-92-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; at 10 - 20℃; for 5.0h;	l-methoxy-3-methyl-2-nitro-4- (trifluoromethyl)benzene was prepared by a procedure similar to that described in "Synthesis of 3, 6-Disubstituted 2-Nitrotoluenes by Methylation of Aromatic Nitro Compounds withDimethylsulfonium Methylide", Kitano, Masafumi, Ohashi Naohito, Synthetic Communications, 30(23), 4247-4254, 2000. To a suspension of NaH (60% by wt. in mineral oil, 362 mg, 9.04 mmol) and trimethylsulfonium iodide (1.84 g, 9.04 mmol) in DMSO (17 ml) and THF (6.7 ml) was added 4-methoxy-3- nitrobenzotrifluoride (1.00 g, 4.52 mmol) as a solution in DMSO (2.7 ml) . The reaction mixture was allowed to stir at 10-200C for 5 hrs . The reaction mixture was quenched by addition to ice water. The aqueous layer was separated and extracted with toluene 7 times. The combined organic extracts were washed with brine, dried over MgSO4, and filtered. The solvent was removed by distillation at reduced pressure. The residue was purified by automated silica gel chromatography (100% hexanes to 98:2 hexanes :ethylacetate) to provide l-methoxy-3-methyl-2-nitro-4- (trifluoromethyl)benzene.

Reference： [1]Patent: WO2006/44823,2006,A2 .Location in patent: Page/Page column 137

33
[ 30314-44-4 ]
[ 2181-42-2 ]
2-t-butyl-2-(4-methylphenyl)-oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; dimethyl sulfoxide;	EXAMPLE 3 Preparation of 2-(t-butyl)-2-(4-methylphenyl)-oxirane STR14 A 2.2 g portion of 61.4% sodium hydride is washed three times with petroleum ether, then 70 ml. of dimethyl sulfoxide added and the mixture heated with stirring to 70 C. and carried to 85 C. by the exotherm after which the mixture is heated at 75 C. for 40 minutes. The resulting mixture is cooled to 0 C. in an ice/salt bath and then under a nitrogen blanket there is added dropwise a solution of 7.0 g. of trimethylsulfonium iodide in 50 ml. of dimethylsulfoxide and 20 ml. tetrahydrofuran while maintaining the temperature below 18 C. To the resulting mixture is then added with stirring under the nitrogen blanket a solution of 3.0 g. of t-butyl p-methylphenyl ketone in 30 ml. of tetrahydrofuran while maintaining the temperature below 10 C. The resulting mixture is stirred at 0 C. for 30 minutes and then at room temperature for 2 hours. The resulting reaction mixture is hen poured onto 400 ml. of water, extracted with methylene chloride, the organic phase washed with water and then brine, dried and evaporated to obtain a yellow oil of 2-(t-butyl)-2-(4-methylphenyl)-oxirane.

Reference： [1]Patent: US4432989,1984,A

34
[ 31739-56-7 ]
[ 2181-42-2 ]
[ 1001053-74-2 ]

Reference： [1]Heterocycles,2007,vol. 71,p. 2717 - 2720

35
[ 2181-42-2 ]
[ 13510-35-5 ]
trimethylsulphonium indium(III) iodide [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1936,vol. 58,p. 908
[2]Gmelin Handbuch der Anorganischen Chemie,Gmelin Handbook: In: MVol., 3.21, page 110 - 113

36
[ 17159-79-4 ]
[ 2181-42-2 ]
[ 171361-65-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 2,8,9-tris(2-methylpropyl)-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane; In acetonitrile; at 0 - 20℃; for 1.5h;Product distribution / selectivity;	Procedure 9b; A mixture of 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (1.14 ml, 3.94 mmol) and acetonitrile (15 ml) was added to a stirred suspension of trimethylsulphonium iodide (0.81 g, 3.97 mmol) and ethyl 4-oxocyclohexanecarboxylate (0.563 g, 3.31 mmol) at 0 0C. The mixture was stirred at 0 0C for 30 minutes then allowed to warm to room temperature and stirred for a further 1 hour. The reaction mixture was concentrated under reduced pressure then diluted with diethyl ether. The resulting suspension was stirred for 30 minutes then filtered and the filter cake was washed with more diethyl ether. The combined ethereal phases were concentrated under reduced pressure and the residue was chromatographed on SiO2 (Biotage 25M column) eluting with a gradient of 5%-15% EtOAc/cyclohexane to give a -60:40, trans:cis mixture of the title compound as a colourless oil (250 mg); <n="30"/>1 H NMR (400 MHz, CDCI3): delta 4.16 (2H both isomers, q), 2.65 (2H trans isomer, s), 2.62 (2H cis isomer, s), 2.35-2.48 (1 H both isomers, m), 1.68-2.14 (6H both isomers, m), 1.37- 1.52 (2H both isomers, m), 1.27 (3H both isomers, t).

Reference： [1]Patent: WO2008/92887,2008,A1 .Location in patent: Page/Page column 28-29

37
[ 1979-36-8 ]
[ 2181-42-2 ]
[ 1037739-44-8 ]

Reference： [1]Synthesis,2008,p. 1404 - 1414

38
[ 2181-42-2 ]
[ 116707-09-6 ]
[ 1073898-04-0 ]

Reference： [1]Synthesis,2008,p. 1404 - 1414

39
[ 2181-42-2 ]
[ 1122-91-4 ]
[ 32017-76-8 ]

Yield	Reaction Conditions	Operation in experiment
81.8%	With potassium hydroxide;	Step 1: The synthesis of 2-(4-bromophenyl)oxirane A mixture of 4-bromobenzaldehyde (2.52 g, 13.6 mmol), trimethylsulfonium iodide (2.87 g, 14.1 mmol), water (0.65 mL, 36.1 mmol) and potassium hydroxide (1.56 g, 27.7 mmol) in acetonitrile (20 mL) was warmed to 55 C. for 4 hours. The resulting solution was partitioned between water and diethyl ether, and the organic layer was washed with water, diluted hydrochloric acid, and brine, and dried over sodium sulfate. Crude product of 2-(4-bromophenyl)oxirane (2.20 g, 81.8% yield) was obtained by removal of organic solvent under reduced pressure, which was used for next reaction without purification. 1H NMR (400 MHz, CDCl3) delta 2.74 (1H, q, J=2.8 Hz), 3.14 (1H, dd, J=4.0 Hz, 5.2 Hz), 3.82 (1H, dd, J=2.4 Hz, 4.0 Hz), 7.15 (2H, d, J=8.4 Hz), 7.47 (2H, d, J=8.8 Hz).
74%	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;	4.2.2 4-Bromostyrene oxide 1m Epoxide 1m was prepared according to a literature procedure. 13 4-Bromobenzaldehyde (1.0 g, 5.4 mmol) and trimethylsulfonium iodide (1.76 g, 8.6 mmol) were dissolved in DMSO (8 mL). Potassium tert-butoxide (0.92 g, 8.2 mmol) was dissolved in 8 mL of DMSO and added to the reaction mixture. Reaction mixture was stirred over night at room temperature under argon. Reaction was quenched by addition of water (16 mL). Reaction mixture was extracted with dichloromethane (3 * 30 mL), combined organic layers were dried over Na2SO4, filtered and evaporated under reduced pressure. Column chromatography (SiO2; hexane-ethyl acetate, 9:1) furnished the pure epoxide 1m (0.79 g, 74%) as a colourless liquid. dH (300 MHz, CDCl3) 2.74 (1H, dd, J1 5.5 Hz, J2 2.5 Hz), 3.13 (1H, dd, J1 5.5 Hz, J2 4.0 Hz), 3.82 (1H, dd, J1 4.0 Hz, J2 2.5 Hz), 7.14 (2H, d, J 8.5 Hz), 7.46 (2H, d, J 8.5 Hz); dC (75 MHz, CDCl3) 51.2, 51.8, 122.0, 127.2, 131.7, 136.8.
66%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 0 - 20℃; for 12.5h;Inert atmosphere;	Sodium hydride (0.95 g, 24 mmol, 60% mineral oil dispersion) was washed with petroleum ether (3 5 mL). The residual petroleum ether was removed under vacuum. Under atmosphere of nitrogen, dry THF (11 mL) and dry DMSO (11 mL) were added and the reaction mixture was cooled in an ice bath. A solution of trimethylsulfonium iodide (2.04 g, 20 mmol) in DMSO (4 mL) was added. After addition, 4-bromobenzaldehyde (3.70 g, 20 mmol) was added in one portion. The reaction mixture was stirred at 0 C for 30 min and at room temperature for an additional 12 h. The reaction mixture was slowly quenched with a mixture of water and ice (20 mL) and extracted with methylene chloride (310 mL). The combined organic extracts were washed with brine (230 mL), dried over potassium carbonate, filtered. The residue was purified by column chromatography (silica gel, PE) to give 2-(4-bromophenyl)oxirane (4e).

	With potassium hydroxide; water; In acetonitrile; at 55℃; for 2.5h;	A mixture of 4"bromobenzaldehyde (intermediate 29, 25.25 g, 136 mmol), trimethylsulfonium iodide (28.7 Ig, 141 mmol), water (6.5 ml, 361 mmol) and potassium hydroxide (15.56 g, 277 mmol) in acetonitrile (140 ml) was warmed to 55 C for 2.5 hours. The resulting solution was partitioned between water and diethyl ether, and the organic layer was washed with water, diluted hydrochloric acid, and brine, and dried over sodium sulfate. Crude product of 2-(4-bromo-phenyl)-oxirane (intermediate 30) was obtained by removal of organic solvent under reduced pressure, which was used for next reaction without purification.
	With potassium hydroxide; water; In acetonitrile; at 55℃; for 2.5h;	A mixture of 4-bromobenzaldehyde (intermediate 2J), 25.25 g, 136 mmol), trimethylsulfonium iodide (28.71g, 141 mmol), water (6.5 ml, 361 mmol) and potassium hydroxide (15.56 g, 277 mmol) in acetonitrile (140 ml) was warmed to 55 0C for 2.5 hours. The resulting solution was partitioned between water and diethyl ether, and the organic layer was washed with water, diluted hydrochloric acid, and brine, and dried over sodium sulfate. Crude product of 2-(4-bromo-phenyl)-oxirane (intermediate 30) was obtained by removal of organic solvent under reduced pressure, which was used for next reaction without purification.
	With water; potassium hydroxide; In acetonitrile; at 55℃; for 4h;	A mixture of 4-bromobenzaldehyde (2.52 g, 13.6 mmol), trimethylsulfonium iodide (2.87 g, 14.1 mmol), water (0.65 mL, 36.1 mmol) and potassium hydroxide (1.56 g, 27.7 mmol) in acetonitrile (20 mL) was warmed to 55 C for 4 hours. The resulting solution was partitioned between water and diethyl ether, and the organic layer was washed with water, diluted hydrochloric acid, and brine, and dried over sodium sulfate. Crude product of 2-(4- bromophenyl)oxirane (2.20 g, 81.8% yield) was obtained by removal of organic solvent under reduced pressure, which was used for next reaction without purification. H NMR (400 MHz, CDC13) delta 2.74 (1H, q, / = 2.8 Hz), 3.14 (1H, dd, J = 4.0 Hz, 5.2 Hz), 3.82 (1H, dd, 7 = 2.4 Hz, 4.0 Hz), 7.15 (2H, d, 7 = 8.4 Hz), 7.47 (2H, d, 7 = 8.8 Hz).

Reference： [1]Tetrahedron,2009,vol. 65,p. 8199 - 8205
[2]Patent: US2018/125821,2018,A1
[3]Chemical Communications,2016,vol. 52,p. 7482 - 7485
[4]Tetrahedron Asymmetry,2016,vol. 27,p. 930 - 935
[5]Chemical Communications,2018,vol. 54,p. 11340 - 11343
[6]Tetrahedron,2018,vol. 74,p. 1613 - 1620
[7]Journal of Organic Chemistry,2019,vol. 84,p. 4443 - 4450
[8]Patent: WO2009/35159,2009,A1 .Location in patent: Page/Page column 28
[9]Patent: WO2009/35162,2009,A1 .Location in patent: Page/Page column 28-29
[10]Patent: WO2017/30814,2017,A1 .Location in patent: Paragraph 00216
[11]Chemical Communications,2017,vol. 53,p. 4308 - 4311

40
[ 426219-51-4 ]
[ 2181-42-2 ]
6,7-dihydro-5H-spiro[imidazo[1,5-a]pyridine-8,2'-oxirane] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; N,N-dimethyl-formamide; at 0 - 60℃; for 18h;	d) 6,7-Dihydro-5H-spiro[imidazo[1,5-a]pyridine-8,2'-oxirane] Sodium hydride (22 mmol) washed with pentane is admixed under argon with 20 ml of dimethyl sulphoxide. The mixture is heated at 60 C. for an hour and then diluted with 5 ml of tetrahydrofuran. The mixture is cooled to 0 C. and a solution of 21 mmol of trimethyl-sulphonium iodide in 5 ml of N,N-dimethylformamide is added at 0 C., after which the mixture is stirred for 10 minutes. A solution of 20 mmol of <strong>[426219-51-4]6,7-dihydro-5H-imidazo[1,5-a]pyridin-8-one</strong> [426219-51-4] in 5 ml of N,N-dimethylformamide is added and the reaction mixture is stirred at 60 C. for 18 hours. The reaction mixture is poured into cold brine and extracted with tert-butyl methyl ether. The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60 F) on the basis of the Rf value.
		Sodium hydride (22 mmol) washed with pentane is admixed under argon with 20 ml of dimethyl sulphoxide. The mixture is heated at 600C for an hour and then diluted with 5 ml of tetrahydrofuran. The mixture is cooled to 0C and a solution of 21 mmol of trimethyl- sulphonium iodide in 5 ml of N.N-dimethylformamide is added at 00C, after which the mixture is stirred for 10 minutes. A solution of 20 mmol of <strong>[426219-51-4]6,7-dihydro-5H-imidazo[1,5-a]pyridin-8-one</strong> [426219-51-4] in 5 ml of N,N-dimethylformamide is added and the reaction mixture is stirred at 600C for 18 hours. The reaction mixture is poured into cold brine and extracted with tert- butyl methyl ether. The combined organic phases are washed with brine, dried with sodium sulphate and evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60F) on the basis of the Rf value.

Reference： [1]Patent: US2009/111840,2009,A1 .Location in patent: Page/Page column 11-12
[2]Patent: WO2006/128853,2006,A1 .Location in patent: Page/Page column 28

41
[ 5381-20-4 ]
[ 2181-42-2 ]
[ 74-89-5 ]
[ 556025-68-4 ]

Yield	Reaction Conditions	Operation in experiment
		Potassium hydroxide (3.11 g) and water (0.12 ML) are added to acetonitrile (50 ML). TRIMETHYLSULFONIUM iodide (5.65 g) and thianapthene-3-carboxaldehyde (4.50 g) are then added. The reaction mixture is heated to 60 C for 4 h. The reaction mixture is allowed to cool to room temperature and is then diluted with Et20 (25 ML). The precipitate is filtered off, and the filtrate is concentrated in vacuo. The resulting crude epoxide (6.20 g) is dissolved in methanol (40 ML) and added to a 2.0 M solution of methyl amine in methanol (100 mL). The reaction mixture is stirred at room temperature for 3 d. The reaction mixture is concentrated in vacuo. The resulting brown oil is PURIFIED VIA COLUMN CHROMATOGRAPHY (CHCL3/METHANOL, 95/5,90/10 ; CHC13/METHANOINI-LOH, 90/10/1) to yield 1.753 g of the title compound as a yellow solid. Physical characteristics. M. p. 98-102C ; 1H NMR (400 MHz, DMSO-d6) 8 7.98-7. 90,7. 51,7. 60, 7.40-7. 33,5. 43,5. 04,2. 80, 2.34 ; MS (ESI+) m/z 208 (M+H) +.

Reference： [1]Patent: WO2004/106345,2004,A2 .Location in patent: Page 47

42
[ 24424-99-5 ]
[ 14473-91-7 ]
[ 2181-42-2 ]
2-(3-bromophenyl)cyclopropane-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%		EXAMPLE 59trans-(+/-)-2- [3 -(Quinoxalin-6-yl)phenyll cyclopropanecarboxylic acidDMAP (220 mg, 1.8 mmol) was added to a solution of <strong>[14473-91-7]3-bromocinnamic acid</strong> (2.00 g, 8.8 mmol) and di-tert-butyl dicarbonate (2.31 g, 10.6 mmol) in THF (7 niL) at O0C. The solution was allowed to warm to room temperature and then stirred for 3 days. The mixture was partitioned between EtOAc (30 mL) and IM hydrochloric acid (10 mL). The organic phase was washed with saturated sodium hydrogencarbonate solution (20 mL) and concentrated in vacuo. The residue was dissolved in DCM (10 mL) and cooled to -78C under nitrogen. A solution of trimethylsulfonium iodide (2.31 g, 10.5 mmol) in DMSO (10 mL) was added, followed by sodium hydride (422 mg, 11.4 mmol). The solution was warmed to 5O0C and stirred for 18 h. The mixture was partitioned between EtOAc (30 mL) and water (30 mL), and the organic phase concentrated in vacuo. The residue was purified by column chromatography to give 2-(3-bromophenyl)cyclopropane- carboxylic acid tert-butyl ester as a yellow oil (2.04 g, 78% over 2 steps). A sample of this material (440 mg, 1.48 mmol) and 6-pinacolatoboranylquinoxaline (380 mg, 1.48 mmol) was dissolved in DME/water (9: 1, 7 mL), and cesium carbonate (975 mg, 3.0 mmol) and Pd(PPh3)4 (80 mg, 0.07 mmol) were added. The mixture was heated to 12O0C in a sealed tube, under microwave irradiation, for 20 minutes. After cooling, the mixture was passed through a silica plug and concentrated in vacuo. The residue was dissolved in DCM (3 mL) and TFA (2.5 mL) added. The mixture was stirred at room temperature for 4 h. The mixture was concentrated in vacuo and the residue partitioned between DCM (10 mL) and 2M sodium hydroxide solution (5 mL). The aqueous phase was neutralized to pH 7 with 2M hydrochloric acid, and extracted with EtOAc (10 mL). The organic phase was concentrated in vacuo to give the title compound as a brown solid (75% purity, 200 mg). A portion of this material was purified by preparative HPLC to yield the title compound (5 mg). deltaH (CD3OD) 8.92 (d, IH), 8.89 (d, IH), 8.30 (s, IH), 8.17 (s, 2H), 7.53 (dd, IH), 7.50 (d, IH), 7.48 (dd, IH), 7.22 (d, IH), 2.60 (m, IH), 1.95 (m. IH), 1.63 (m, IH), 1.48 (m, IH). LCMS (ES+) 291.3 (M+H)+, RT 2.99 minutes.

Reference： [1]Patent: WO2010/52448,2010,A2 .Location in patent: Page/Page column 82-83

43
[ 53014-84-9 ]
[ 2181-42-2 ]
[ 145908-63-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 15 Preparation of 2-methyl-5-(oxiran-2-yl)py?dme [0380] The title compound was prepared by following general procedure 3 DMSO (4mL) was added to NaH 60% dispersion in oil (0 314 g, 7 8 mmol, 1 3 equiv ) and heated to 65 0C for 1 h THF (1OmL) was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 2 g, 5 9 mmol, 1 equiv ) was added and stirred for 10 mm and then a solution of 6-methylmcotmaldehyde (0 720 g, 5 9 mmol, 1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h, the product was detected by LCMS The reaction mixture was poured into ice water and the product was extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to get the crude product 2-methyl-5-(oxiran-2-yl)py?dme (1 1 g crude)
		Example 19A[0427] DMSO (4 mL) was added to NaH 60% dispersion in oil (0.314 g, 7.8 mmol, 1.3 eq.) and heated it to 65 0C for 1 h. THF (10 mL) was added at the same temperature and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1.2 g, 5.9 mmol, 1 eq.) was added and stirred for 10 min and solution of 6- methylnicotinaldehyde (0.72Og, 5.9mmol,leqv) in THF was added dropwise. After complete of addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted in diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get product 2-methyl-5-(oxiran-2- yl)pyridine (1. Ig).

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 251-252
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 244

44
[ 2923-66-2 ]
[ 2181-42-2 ]
[ 1147939-72-7 ]

Yield	Reaction Conditions	Operation in experiment
		Example 24 Preparation of 2-(3-chloro-4-fluorophenyl)-2-methyloxirane[0389] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(3-chloro-4-fluorophenyl)ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 28A [0445] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temperature and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(3-chloro-4-fluorophenyl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 254-255
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 249-250

45
[ 2181-42-2 ]
[ 386704-12-7 ]
[ 1225223-41-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 33 Preparation of 2-(trifluoromethyl)-5-(oxiran-2-yl)py?dme[0398] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of 6-(t?fluoromethyl)py?dme-3-carbaldehyde (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 37A [0462] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temp, and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of <strong>[386704-12-7]6-(trifluoromethyl)pyridine-3-carbaldehyde</strong> (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 rnL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 257
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 254-255

46
[ 51788-77-3 ]
[ 2181-42-2 ]
[ 1147939-78-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 19 Preparation of 2-(2.4.6-trifluorophenyl)-2-methyloxirane[0384] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(2,4,6-t?fluorophenyl)ethanone (1 equiv ) in THF was added dropwise After completion of this addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted with diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 23A [0435] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temp, and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(2,4,6-trifluorophenyl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 253
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 246-247

47
[ 2181-42-2 ]
[ 39870-05-8 ]
[ 1225226-71-0 ]

Yield	Reaction Conditions	Operation in experiment
		Trimethylsulfonium iodide (3.34 g, 16.3 mmol) was dissolved in DMF(20 mL) and stirred at RT for 5 min. Sodium hydride (600 mg, 25 mmol ) was added portionwise at the same temperature and stirred for 15 min. 4- Acetyl pyrimidine (1 g, 8.1 mmol) in 0.5 mL DMSO was added dropwise and the reaction mixture stirred for 1 h. After completion of reaction, the mixture was poured into ice-cold water and extracted with Ether (3x). The combined organic layer was washed with water several times followed by brine, and dried over sodium sulfate, then evaporated to provide 600 mg of 4-(2-Methyl-oxiranyl)-pyrimidine. 1H NMR (CDCl3, freebase) d (ppm): 9.15 (s, IH), 8.7 (d, IH), 7.35 (d, IH), 2.95 (d, IH), 2.88 (d, IH), 1.8 (s, 3H).

Reference： [1]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 343

48
[ 36357-38-7 ]
[ 2181-42-2 ]
[ 1147939-34-1 ]

Yield	Reaction Conditions	Operation in experiment
		Example 37 Preparation of 2-methyl-5-(2-methyloxiran-2-yl)py?dme[0402] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(6-methylpy?dm-3-yl) ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 41 A [0470] DMSO was added to NaH (1 equiv) and heated to 650C for 1 h. THF was added at same temp, and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(6-methylpyridin-3-yl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 258
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 256-257

49
[ 358780-14-0 ]
[ 2181-42-2 ]
[ 1147939-55-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 32 Preparation of 2-(t?fluoromethyl)-5-(2-methyloxiran-2-yl)pyridme[0397] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(6-(t?fluoromethyl)py?dm-3-yl)ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 36 A [0460] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temperature and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(6-(trifluoromethyl)pyridin-3-yl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product.

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 257
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 253-254

50
[ 772-31-6 ]
[ 2181-42-2 ]
[ 1147939-86-3 ]

Yield	Reaction Conditions	Operation in experiment
		Example 34 Preparation of 2-cvclopropyl-2-(4-fluorophenyl)oxirane[0399] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C Tϖmethylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of cyclopropyl (4-fluorophenyl) methanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 50 mL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 38 A [0464] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temp, and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of <strong>[772-31-6]cyclopropyl(4-fluorophenyl)methanone</strong> (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product. 1H NMR (CDCl3, freebase) d (ppm): 7.05 (m, 4H), , 2.9 (d, IH), 2.7 (d, IH), 0.87 (m, IH), 0.61 (m, 2H), 0.45 (m, 2H).

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 257
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 255

51
[ 369-33-5 ]
[ 2181-42-2 ]
2-(3,4-difluorophenyl)-2-methyl-oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 23 Preparation of 2-(3,4-difluorophenyl)-2-methyloxirane[0388] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(3,4-difluorophenyl)ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product
		Example 27A 0443] DMSO was added to NaH (1 equiv) and heated to 65 0C for 1 h. THF was added at same temperature and heated for another 10 min. After 10 min, reaction mixture was cooled to 0 0C. Trimethylsulfonium iodide (1 equiv) was added and stirred for 10 min after which the solution of l-(3,4-difluorophenyl)ethanone (1 equiv) in THF was added dropwise. After complete addition, reaction mixture was stirred at RT for 2 h. Product was detected by LCMS. Reaction mixture was poured in ice water. Product was extracted with diethyl ether (4x50 mL), dried over sodium sulfate and concentrated under vacuum at 25 0C to get the product. 1H NMR (CDCl3, freebase) d (ppm): 7.17 (m, 3H), 2.99 (d, IH), 2.79 (d, IH), 1.71 (s, 3H).

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 254
[2]Patent: WO2010/51501,2010,A1 .Location in patent: Page/Page column 249

52
[ 36357-38-7 ]
[ 2181-42-2 ]
[ 1189785-18-9 ]

Yield	Reaction Conditions	Operation in experiment
		Example 38 Preparation of 2-methyl-5-(2-methyloxiran-2-yl)py?midme[0403] The title compound was prepared by following general procedure 3 DMSO was added to NaH (1 equiv ) and heated to 65 0C for 1 h THF was added at the same temperature and heated for another 10 mm After 10 mm , the reaction mixture was cooled to 00C T?methylsulfomum iodide (1 equiv ) was added and stirred for 10 mm after which the solution of l-(2-methylpy?midm-5-yl) ethanone (1 equiv ) in THF was added dropwise After complete addition, the reaction mixture was stirred at RT for 2 h The product was detected by LCMS and the reaction mixture was poured into ice water, extracted in diethyl ether (4 x 5OmL), dried over Na2SO4 and concentrated at 25 0C to obtain the product

Reference： [1]Patent: WO2010/51503,2010,A1 .Location in patent: Page/Page column 258-259

53
[ 2181-42-2 ]
[ 82543-16-6 ]
[ 1015063-84-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium tert-butylate; In tetrahydrofuran; dimethyl sulfoxide; at -15℃;	Intermediate (1) (5 g, 15.13 mmol) was dissolved in DMSO/THF (50 mL/50 mL), treated with trimethylsulfonium iodide (4.63 g, 22.70 mmol), and the mixture was chilled to -15 C. The mixture was treated portion wise with potassium t-butoxide (5.03 g, 43.88 mmol). The mixture was stirred at -15 C for 45 min and then poured into ice/water (200 mL). The aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water (2×) and brine, dried over sodium sulfate, and filtered. Evaporation of the solvent gave 5.11 g (98%) of oxirane (12f) as a stable foam.

Reference： [1]Patent: US2010/261896,2010,A1 .Location in patent: Page/Page column 15

54
[ 29943-42-8 ]
[ 2181-42-2 ]
[ 185-72-8 ]

Yield	Reaction Conditions	Operation in experiment
59%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 0 - 20℃; for 18h;Inert atmosphere;	Under nitrogen 6.6 g sodiumhydride (60% in mineral oil) are suspended in 90 ml tetrahydrofurane and cooled to 0 C. 91.7 Trimethylsulfonium iodide are added in portions. To this mixture a solution of 15 g dihydro-2H-pyran-4(3H)-one in 300 ml dimethylsulfoxide and 60 ml tetrahydrofurane is added dropwise. Afterwards the mixture is warmed to room temperature and stirred for 18 hours. The mixture is then poured into 1.2 l icewater and extracted for three times with diethylether. The combined organic phases are washed with brine and dried with sodium sulphate. Evaporation of the solvents in vacuo gives the product.Yield: 10.15 g (59% of theory)Rf-value: 0.47 (silica gel, petrole ether/ethylacetate 1:1)
59%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 0 - 20℃; for 18h;Inert atmosphere;	Intermediate 2: (S)-9-(tert-Butyldimethylsilyloxy)-4-isopropyl-9-hydroxy-,7,7-(ethan-1 ,2-diyl)-2',3',5',6,6',7,8,9- octahydro-3H-spiro[furo[3,4-c]quinoline-1 ,4'-pyran]-3-one Stepl : 1 ,6-Dioxaspiro[2.5]octane Under nitrogen 6,6 g sodiumhydride (60% in mineral oil) are suspended in 90 ml tetrahydrofurane and cooled to 0C. 91 ,7 Trimethylsulfonium iodide are added in portions. To this mixture a solution of 15 g dihydro-2H-pyran-4(3H)-one in 300 ml dimethylsulfoxide and 60 ml tetrahydrofurane is added dropwise. Afterwards the mixture is warmed to room temperature and stirred for 18 hours. The mixture is then poured into 1 ,2 I icewater and extracted for three times with diethylether. The combined organic phases are washed with brine and dried with sodium sulphate. Evaporation of the solvents in vacuo gives the product. Yield: 10,15 g (59 % of theory) Rf-value: 0,47 (silica gel, petrole ether/ethylacetate 1 :1 )
59%	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; mineral oil; at 0 - 20℃; for 18h;Inert atmosphere;	Step 1: 1,6-Dioxaspiro[2.5]octane Under nitrogen 6.6 g sodiumhydride (60% in mineral oil) are suspended in 90 ml tetrahydrofurane and cooled to 0 C. 91.7 Trimethylsulfonium iodide are added in portions. To this mixture a solution of 15 g dihydro-2H-pyran-4(3H)-one in 300 ml dimethylsulfoxide and 60 ml tetrahydrofurane is added dropwise. Afterwards the mixture is warmed to room temperature and stirred for 18 hours. The mixture is then poured into 1.2 l icewater and extracted for three times with diethylether. The combined organic phases are washed with brine and dried with sodium sulphate. Evaporation of the solvents in vacuo gives the product. Yield: 10.15 g (59% of theory) Rf-value: 0.47 (silica gel, petrole ether/ethylacetate 1:1)

26%		Step 1. Synthesis of Intermediate 6-2. To a mixture of trimethylsulfoxonium iodide (12.2 g, 59.8 mmol) in DMSO (40 mL) at 5 C under N2 , NaH (2.38 g, 60% in mineral oil, 59.8 mmol) was added portionwise and the mixture was stirred at 5 C for 30 mins. Intermediate 6-1 (5 g, 49.9 mmol) in DMSO (40 mL) was added dropwise maintaining the temperature below 15 C and the reaction mixture was stirred at 15 C for 20 hrs. The reaction was quenched at 10 C with water (200 mL) and extracted with MTBE (2 x 200 mL). The combined organic phases were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated and the resulting residue was purified by silica gel chromatography (0%~50% EtOAc in PE) to afford Intermediate 6-2 (1.5 g, 26 %) as colorless oil. (0332) 1H NMR (400 MHz, CDCl3) delta 3.93-3.76 (m, 4H), 2.69 (s, 2H), 1.94-1.81 (m, 2H), 1.58-1.48 (m, 2H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	Step 1. Synthesis of 1,6-dioxaspiro[2.5]octane; To a clear solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in 20 ml of DMSO was added dihydro-2H-pyran-4(3H)-one (11.0 g, 10 mmol) with stirring. To this mixture, under nitrogen, was then slowly added KOtBu (1.68 g, 15 mmol) in 15 ml of DMSO. The resulting solution was then stirred overnight at ambient temperature. Water (50 ml) was slowly added to the mixture, and the resulting mixture was extracted with diethyl ether (3×20 ml). The ether layers were combined, dried and concentrated in vacuo to yield 650 mg of the crude product. 1H NMR (300 MHz, CHLOROFORM-d) delta ppm 1.44-1.62 (m, 2H) 1.76-1.98 (m, 2H) 2.70 (s, 2H) 3.70-3.98 (m, 4H).
	In dimethyl sulfoxide; at 20℃;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude l,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. 1H NMR (300 MHz, chloroform-d) delta .[rhorhoetaiota]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude 1,6- dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. 1H NMR (300 MHz, chloroform-d) 5.[ppm]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 - 3.98 (m, 4 H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude l,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. 1H NMR (300 MHz, chloroform-d) 5.[ppm]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).
	With tert-butyl alcohol; In dimethyl sulfoxide; at 20℃;Inert atmosphere;Product distribution / selectivity;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 ml_) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 ml_) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude 1 ,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. H NMR (300 MHz, chloroform-d) delta [ppm]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off andconcentrated under reduced pressure providing crude 1 ,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. H NMR (300 MHz, chloroform- d) delta [ppm]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	Synthesis of intermediate (4-methoxytetrahydro-2H-pyran-4-yl) methyl 4- methylbenzen (Intermediate O)Step 1. Synthesis of 1 ,6-dioxaspiro[2.5]octaneTo a clear solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in 20 ml of DMSO was added dihydro-2H-pyran-4(3H)-one (1.0g, 10 mmol) with stirring. To this mixture, under nitrogen, was then slowly added KOtBu (1.68g, 15 mmol) in 15 ml of DMSO. The resulting solution was then stirred overnight at ambient temperature.Water (50ml) was slowly added to the mixture, and the resulting mixture was extracted with diethyl ether (3x20ml). The ether layers were combined, dried and concentrated in vacuo to yield 650 mg of the crude product. 1 H NMR (300 MHz, CHLOROFORM-d) . ppm 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).
	With potassium tert-butylate; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1 .0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1 .68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude 1 ,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. 1 H NMR (300 MHz, chloroform-d) 5.[ppm]: 1 .44 - 1 .62 (m, 2 H) 1 .76 - 1 .98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).

Reference： [1]Patent: US2012/46304,2012,A1 .Location in patent: Page/Page column 178
[2]Patent: WO2013/24130,2013,A1 .Location in patent: Page/Page column 46; 47
[3]Patent: US2013/210850,2013,A1 .Location in patent: Paragraph 0269-0272
[4]Patent: WO2017/173358,2017,A1 .Location in patent: Paragraph 00136
[5]Patent: US2011/28492,2011,A1 .Location in patent: Page/Page column 24
[6]Patent: WO2011/26904,2011,A1 .Location in patent: Page/Page column 63-64
[7]Patent: WO2012/66065,2012,A1 .Location in patent: Page/Page column 83
[8]Patent: WO2012/66070,2012,A1 .Location in patent: Page/Page column 90
[9]Patent: WO2012/101065,2012,A2 .Location in patent: Page/Page column 86-87
[10]Patent: WO2012/101063,2012,A1 .Location in patent: Page/Page column 120
[11]Patent: WO2012/101066,2012,A1 .Location in patent: Page/Page column 73; 97
[12]Patent: WO2012/101064,2012,A1 .Location in patent: Page/Page column 161

55
[ 1268599-55-8 ]
[ 2181-42-2 ]
[ 5345-42-6 ]

Reference： [1]European Journal of Organic Chemistry,2011,p. 295 - 301

56
[ 4560-41-2 ]
[ 2181-42-2 ]
[ 61535-21-5 ]

Reference： [1]European Journal of Organic Chemistry,2011,p. 295 - 301

57
[ 91-23-6 ]
[ 2181-42-2 ]
[ 5345-42-6 ]

Reference： [1]European Journal of Organic Chemistry,2011,p. 295 - 301

58
[ 2181-42-2 ]
[ 130753-13-8 ]
[ 1073923-19-9 ]

Yield	Reaction Conditions	Operation in experiment
		Example 2: Synthesis of benzyl SH-spirofdelta-azabicyclofS^.lJoctane-S^'-oxiraneJ-delta- carboxylate (compound 2).; To a suspension of sodium hydride (34.5 g, 143 mmol, 50% suspension in hexane) in DMF (800 mL) was added, a solution of trimethyl sulfonium iodide (118.9 g, 0.58 mol) in DMF (800 mL), over a period of 1 Vi h. After 15 minutes at room temperature, a solution of <strong>[130753-13-8]benzyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate</strong> (1, 100.0 g, 0.38 mol) in DMF (800 mL) was added. After stirring for 1 h, the reaction mixture was poured onto ice-cold water (6.4 L) and then extracted with ethyl acetate (2.0 L x 3). Organic phases were combined, washed with water (1.0 L x 3), followed by brine (1.0 L) and then dried over anhydrous sodium sulphate. It was filtered, the filtrate evaporated and the residue was directly used for the next step. Yield: 105 g. TLC, Rf (Etaexane/Ethyl Acetate 30%) = 0.35. IR cm"1 (CHCl3) 2950, 1698, 1414, 1322, 1204, 1097, 1008, 760. 1HNMR (400 MHz, CDCl3): delta 7.32 (m, 5H), 5.15 (s, 2H), 4.41 (m, 2H), 2.43 (s, 2H), 2.38 (m, 2H), 2.13-1.99 (m, 4H), 1.22 (m, 2H). MS: 274 (M+ 1)+.

Reference： [1]Patent: WO2011/18796,2011,A1 .Location in patent: Page/Page column 19

59
[ 2181-42-2 ]
[ 642-31-9 ]
[ 61695-73-6 ]

Yield	Reaction Conditions	Operation in experiment
83%	With water; potassium hydroxide; In acetonitrile; at 60℃; for 24h;Inert atmosphere; Schlenk technique;	A solution of anthracene-9-carbaldehyde (1.03 g; 5 mmol; 1.00 eq.) in acetonitrile trimethylsulfonium iodide (1.22 g; 6 mmol; 1.20 eq.) and potassium hydroxide (0.56 g; 10 mmol; 2 eq.) was added to a Schlenk flask and degassed by three freeze-pump-thaw cycles. Deionized water (0.05 g; 2.8 mmol; 0.56 eq.) was placed to the N2-purged flask and the solution was then stirred at 60C for 24h. The solvent was removed in a vacuum and the product mixture was diluted with diethyl ether and washed several times with deionized water and sodium bicarbonate solution (1:1). Finally the solution was filtered over celite and dried in a vacuum at 45C to afford 0.91 g of a yellowish solid (83% of the theoretical yield), which was analysed by 1H NMR spectroscopy (delta, 400MHz, 20C, CDCl3) 8.49-8.45 (m, 2H, an1,10), 8.03-8.01 (d, 2H, an4,5), 7.57-7.47 (m, 4H, an2,3,6,7), 4.72 (s, 1H, an-CH-O-), 3.59, 3.06 (s, 2H, -CH2) ppm and 13C NMR spectroscopy (delta, 125MHz, 20C, CDCl3) 131.30 (1C, an9), 130.41 (1C, an9a), 129.05 (2C, an5,4), 128.46 (2C, an4a,10a), 128.05 (1C, an10), 126.25 (2C, an6,3), 125.15 (2C, an7,2), 124.75 (2C, an8,1), 50.31 (1C, an-CH-O), 49.28 (1C, O-CH2) ppm.

Reference： [1]Polymer,2015,vol. 80,p. 76 - 87
[2]Journal of the American Chemical Society,2011,vol. 133,p. 4710 - 4713

60
[ 885167-81-7 ]
[ 2181-42-2 ]
[ 1400997-49-0 ]

Yield	Reaction Conditions	Operation in experiment
26%		EXAMPLE 120(RS)-N-(5-Bromopyridin-2-yl)-3-methyl-5-(morpholin-2-yl)pyridin-2-aminea) (RS)-2-Bromo-3-methyl-5-(oxiran-2-yl)pyridineTo a stirred suspension of sodium hydride (1.01 g) in THF (20 ml) was added dropwise over 5 min a solution of trimethylsulfonium iodide (4.69 g) in DMSO (20 ml). The reaction mixture was stirred for 5 min and then cooled to 0 C. A solution of <strong>[885167-81-7]6-bromo-5-methylnicotinaldehyde</strong> (4.6 g, CAS 885167-81-7) in THF (15 ml) was added dropwise. The reaction mixture was stirred at 0 C. for 30 min and then at room temperature overnight. The mixture was then poured into EtOAc/Et2O (1:1) and washed with saturated brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-bromo-3-methyl-5-(oxiran-2-yl)pyridine (1.26 g, 26%) as a colourless oil. MS (ISP): 216.1 ([{81 Br}M+H]+), 214.1 ([{79Br}M+H]+).
26%		To a stirred suspension of sodium hydride (1.01 g) in THF (20 ml) was added dropwise over 5 min a solution of trimethylsulfonium iodide (4.69 g) in DMSO (20 ml). The reaction mixture was stirred for 5 minand then cooled to 0 C. A solution of <strong>[885167-81-7]6-bromo-5-methylnicotinaldehyde</strong> (4.6 g, CAS 885167-81-7) in THF (15 ml) was added dropwise. The reaction mixture was stirred at 0 C for 30 min and then at room temperature overnight. The mixture was then poured into EtOAc/Et20 (1: 1) and washed with saturated brine. The organic layer was dried over Na2S04 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; gradient: 0% to 50% EtOAc in hexanes) to afford (RS)-2-bromo-3-methyl-5-(oxiran-2- yl)pyridine (1.26 g, 26%) as a colourless oil. MS (ISP): 216.1 ([{ 81Br}M+H]+), 214.1([{79Br}M+H]+).

Reference： [1]Patent: US2012/245172,2012,A1 .Location in patent: Page/Page column 56
[2]Patent: WO2012/126922,2012,A1 .Location in patent: Page/Page column 100; 101

61
[ 32161-06-1 ]
[ 2181-42-2 ]
[ 1399360-62-3 ]

Yield	Reaction Conditions	Operation in experiment
60%		Example 70[0203] Trimethylsulfoxonium iodide (550mg, 2.5mmol) was dissolved in anhydrous dimethyl sulfoxide (4 mL) under the protection of argon, and then sodium hydride (lOOmg, 2.5mmol) was added. The reaction mixture was stirred violently at room temperature for 30 min. A solution made by dissolving l-acetylpiperidin-4-one (141mg, l .Ommol) in dimethyl sulfoxide (0.5 mL) was added slowly to the reaction mixture by a syringe. The reaction temperature was then allowed to increase to 60 and stirred for 40 min. Water was added to quench the reaction and the mixture was extracted with ethyl acetate (30mLx2). The combined organic layer was dried over Na2S04 and the solvent was removed under reduced pressure. The residue was purified through a flash silica gel chromatography (petroleum ether/ethyl acetate=5: l) to afford a colorless oil (93mg, 60%). 1H NMR (500MHz, CD3OD), 51.48 (m, IH), 1.55 (m, IH), 1.82 (m, IH), 1.91 (m, IH), 2.16 (s, 3H), 2.75 (s, 2H), 3.48 (m, IH), 3.62 (s, IH), 3.74 (m, IH), 3.98 (m, IH); EM(IES-EM): m/z 156[M++1] .

Reference： [1]Patent: WO2012/122264,2012,A1 .Location in patent: Page/Page column 95

62
[ 2181-42-2 ]
[ 195257-62-6 ]
[ 338956-97-1 ]

Yield	Reaction Conditions	Operation in experiment
93%		To a solution of trimethylsulfonium iodide (5.8 g, 28.84 mmol) in THF (40 mL) at -20 C was added n-BuLi (1.6 M in hexane, 17.2 mL, 27.4 mmol) dropwise and the resulting solution was stirred for 1 h at -20 C. After being stirred for 1 h, a solution of epoxide 8 (1.5 g, 7.21 mmol) in THF (10 mL) was added. The resultant cloudy suspension was allowed to slowly warm to 25 C over 1 h and stirred for another 1 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with water. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (10% EtOAc/hexanes) gave 1.5 g (93%) of allylic alcohol 4 as a yellow oil. (c 1.8, CHCl3); IR (KBr): 3426, 2922, 2859, 1613, 1514, 1465, 1249, 1093, 820 cm-1; 1H NMR (300 MHz, CDCl3): delta = 7.26 (d, J = 8.83 Hz, 2H), 6.88 (d, J = 8.83 Hz, 2H), 5.91-5.84 (m, 1H), 5.27 (d, J = 16.5, 1H), 5.1 (d, J = 9.93 Hz, 1H), 4.45 (s, 2H), 4.36-4.31 (m, 1H), 3.81 (s, 3H), 3.71-3.66 (m, 1H), 3.64-3.59 (m, 1H), 1.89-1.77 (m, 2H); 13C NMR (75 MHz, CDCl3): delta = 159.2, 140.5, 129.9, 129.2, 114.2, 113.7, 72.8, 71.7, 67.9, 55.1, 36.2; ESI-HRMS: m/z [M+Na]+ calcd for C13H18O3Na: 245.11504; found: 245.11482.

Reference： [1]Tetrahedron Asymmetry,2013,vol. 24,p. 594 - 598
[2]European Journal of Organic Chemistry,2012,p. 4910 - 4913
[3]Organic and Biomolecular Chemistry,2013,vol. 11,p. 3355 - 3364
[4]European Journal of Organic Chemistry,2013,p. 4586 - 4593

63
[ 2181-42-2 ]
[ 197229-94-0 ]
[ 1000376-42-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With sodium hydride; In tetrahydrofuran; at 25℃; for 2h;	To a stirred solution of trimethylsulfonium iodide (7.98 g, 39.12 mmol) in dry THF (90 mL) was added NaH (1.38 g, 60.18 mmol) at 25 C. After 30 min, epoxide 15 (6.5 g, 30.09 mmol) in dry THF (15 mL) was added dropwise and the reaction mixture was stirred for 2 h. After completion of the reaction (monitored by TLC), it was quenched with water and extracted with diethyl ether (3 × 100 mL). The combined extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was then purified by column chromatography using petroleum ether/ EtOAc (8:2 v/v) to give allylic alcohol 16 (6.0 g) as a colorless liquid. Yield: 87%; [alpha]25D==-0.7 [alpha]D25==-0.7 (c 0.6, CHCl3); IR (CHCl3): upsilonmax 3354, 2956, 1471, 1443, 1388, 1361, 1255, 1104, 1005, 969, 939, 837, 736, 692 cm-1; 1H NMR (200 MHz, CDCl3): delta 0.02 (s, 6H), 0.84 (s, 9H), 1.54-1.60 (m, 4H), 2.61 (br s, 3H), 3.56-3.62 (t, J = 6.0 Hz, 2H), 4.06 (m, 1H), 4.99-5.23 (m, 2H), 5.71-5.88 (m, 1H); 13C NMR (50 MHz, CDCl3): delta -5.3, 18.3, 26.0, 28.7, 34.4, 63.3, 72.5, 114.3, 141.2; Anal. Calcd for C12H26O2Si requires C, 62.55; H, 11.37. Found: C, 62.50; H, 11.46%.
6 g		[00055] To a stirred solution of trimethylsulfonium iodide (7.98 g, 39.12 mmol) in dry DMSO (90 mL) was added NaH (1.38 g, 60.18 mmol) at 25 C. After 30 mm, epoxide 5b(6.5 g, 30.09 mmol) in dry DMSO (15 mL) was introduced drop-wise and the reaction mixture stirred for 2 h. After completion of the reaction &s monitored by TLC, it was quenched with water and extracted with diethyl ether (3 x 100 mL). The combined extracts were washed with brine, dried over anhydrous. Na2SO4 and concentrated under reduced pressure. The crude product was then purified by column chromatography using petroleum ether/EtOAc (8:2 v/v) to give allylic alcohol (6.0 g) as a colorless liquid.NOTBSOHJR (CHCI3): 692, 776, 837, 939, 969, 1005, 1104, 1255, 1361, 1388, 1443, 1471, 2956,3354 cm?; ?H NMR (200 MHz, CDCI3): oe 0.02 (s, 6H), 0.84 (s, 9H), 1.54-1.60 (m, 4H),2.61 (hr s, 3H), 3.56-3.62 (t, J=6 Hz 2H), 4.06 (m, 1H), 4.99-5.23 (m, 2H), 5.71-5.88 (m,1H); 13C NMR (50 MHz, CDCI3): oe -5.32, 18.38, 26.00, 28.77,34.42, 63.37, 72.59,114.30, 141.29;
6 g		To a stirred solution of trimethylsulfonium iodide (7.98 g, 39.12 mmol) in dry DMSO (90 mL) was added NaH (1.38 g, 60.18 mmol) at 25 C. After 30 min, epoxide 5b (6.5 g, 30.09 mmol) in dry DMSO (15 mL) was introduced drop-wise and the reaction mixture stirred for 2 h. After completion of the reaction as monitored by TLC, it was quenched with water and extracted with diethyl ether (3*100 mL). The combined extracts were washed with brine, dried over anhydrous. Na2SO4 and concentrated under reduced pressure. The crude product was then purified by column chromatography using petroleum ether/EtOAc (8:2 v/v) to give allylic alcohol (6.0 g) as a colorless liquid. IR (CHCl3): 692, 776, 837, 939, 969, 1005, 1104, 1255, 1361, 1388, 1443, 1471, 2956, 3354 cm-1; 1H NMR (200 MHz, CDCl3): delta 0.02 (s, 6H), 0.84 (s, 9H), 1.54-1.60 (m, 4H), 2.61 (br s, 3H), 3.56-3.62 (t, J=6 Hz 2H), 4.06 (m, 1H), 4.99-5.23 (m, 2H), 5.71-5.88 (m, 1H); 13C NMR (50 MHz, CDCl3): delta -5.32, 18.38, 26.00, 28.77, 34.42, 63.37, 72.59, 114.30, 141.29;

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 1534 - 1541
[2]Patent: WO2014/37964,2014,A2 .Location in patent: Paragraph 00055
[3]Patent: US2015/210665,2015,A1 .Location in patent: Paragraph 0086; 0127; 0128

64
[ 1419875-45-8 ]
[ 2181-42-2 ]
[ 1419875-46-9 ]

Yield	Reaction Conditions	Operation in experiment
97%		To a solution of sodium hydride (35.72 g, 1.49 mol) in THF (1L) and dry DMSO (2L) was added under argon drop wise at 5C a solution of trimethylsulfonium iodide (290.5 g, 1 .42 mol) in dry DMSO (2 L). The mixture was stirred 1 hour at 5C followed by a dropwise addition of 1-[2-chloro-4-(4-chlorophenoxy)phenyl]propan-1-one (199.0 g, 0.65 mol) in DMSO (500 mL). The resulting mixture was then warmed to room temperature overnight and quenched with an aqueous solution of ammonium chloride and iced water, and then extracted with MTBE. The organic solvents were washed with water, dried and evaporated to give 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-ethyl-oxirane as a yellowish solid (216.0 g, 97%). 1H-NMR (CDCl3; 400 MHz) D D (ppm)= 0.9 (t, 3H); 1.75 (m, 1H); 2.10 (m, 1H); 2.80 (d, 1H); 3.05 (d, 1H); 6.85 (d, 1H); 6.95 (m, 3H); 7.30 (d, 2H); 7.40 (d, 1H).
97%		Step 2: To a solution of sodium hydride (35.72 g, 1 .49 mol) in THF (1 L) and dry DMSO (2L) was added under argon drop wise at 5C a solution of trimethylsulfonium iodide (290.5 g, 1.42 mol) in dry DMSO (2 L). The mixture was stirred 1 hour at 5C followed by a dropwise addition of 1 -[2-chloro-4-(4-chlorophenoxy)phenyl]propan-1 -one (199.0 g, 0.65 mol) in DMSO (500 ml_). The resulting mixture was then warmed to room temperature overnight and quenched with an aqueous solution of ammonium chloride and iced water, and then extracted with MTBE. The organic solvents were washed with water, dried and evaporated to give 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-ethyl- oxirane as a yellowish solid (216.0 g, 97%). 1H-NMR (CDCI3; 400 MHz) D D(ppm)= 0.9 (t, 3H); 1 .75 (m, 1 H); 2.10 (m, 1 H); 2.80 (d, 1 H); 3.05 (d, 1 H); 6.85 (d, 1 H); 6.95 (m, 3H); 7.30 (d, 2H); 7.40 (d, 1 H).
97%		Step 2 To a solution of sodium hydride (35.72 g, 1 .49 mol) in THF (1 L) and dry DMSO (2L) was added under argon drop wise at 5C a solution of trimethylsulfonium iodide (290.5 g, 1.42 mol) in dry DMSO (2 L). The mixture was stirred 1 hour at 5C followed by a dropwise addition of 1 -[2-chloro-4-(4-chlorophenoxy)phenyl]propan-1 -one (199.0 g, 0.65 mol) in DMSO (500 ml_). The resulting mixture was then warmed to room temperature overnight and quenched with an aqueous solution of ammonium chloride and iced water, and then extracted with MTBE. The organic solvents were washed with water, dried and evaporated to give 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-ethyl- oxirane as a yellowish solid (216.0 g, 97%). 1 H-NMR (CDCI3; 400 MHz) D D(ppm)= 0.9 (t, 3H); 1 .75 (m, 1 H); 2.10 (m, 1 H); 2.80 (d, 1 H); 3.05 (d, 1 H); 6.85 (d, 1 H); 6.95 (m, 3H); 7.30 (d, 2H); 7.40 (d, 1 H).

97%

Step 2 To a solution of sodium hydride (35.72 g, 1.49 mol) in THF (1 L) and dry DMSO (2 L) was added under argon drop wise at 5 C. a solution of trimethylsulfonium iodide (290.5 g, 1.42 mol) in dry DMSO (2 L). The mixture was stirred 1 hour at 5 C. followed by a dropwise addition of 1-[2-chloro-4-(4-chlorophenoxy)phenyl]propan-1-one (199.0 g, 0.65 mol) in DMSO (500 mL). The resulting mixture was then warmed to room temperature overnight and quenched with an aqueous solution of ammonium chloride and iced water, and then extracted with MTBE. The organic solvents were washed with water, dried and evaporated to give 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-ethyl-oxirane as a yellowish solid (216.0 g, 97%). 1H-NMR (CDCl3; 400 MHz) (ppm)=0.9 (t, 3H); 1.75 (m, 1H); 2.10 (m, 1H); 2.80 (d, 1H); 3.05 (d, 1H); 6.85 (d, 1H); 6.95 (m, 3H); 7.30 (d, 2H); 7.40 (d, 1H).

Reference： [1]Patent: WO2013/10862,2013,A1 .Location in patent: Page/Page column 44; 45
[2]Patent: WO2013/24075,2013,A1 .Location in patent: Page/Page column 69
[3]Patent: WO2013/24076,2013,A1 .Location in patent: Page/Page column 71
[4]Patent: US2014/162876,2014,A1 .Location in patent: Paragraph 0277

65
[ 119851-28-4 ]
[ 2181-42-2 ]
2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-methyloxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; dimethyl sulfoxide; at 5 - 20℃; for 1.0h;	DMSO (150 ml.) was added dropwise to a mixture of sodium hydride (22 g) in THF (600 ml_). After completion of the addition a solution of trimethylsulfonium iodide (171 g) in DMSO (300 ml.) was added slowly at 5 C whereupon a solution of 1 -[2-chloro-4- (4-chlorophenoxy)phenyl]ethanone (107 g) in DMSO (300 ml.) was added carefully. The mixture was stirred for 1 h at room temperature and dil. NH4CI solution was added. The mixture was extracted with MTBE (3 x) and the combined orgainc phases were washed with water, dried and evaporated to obtain the desired compound that was used without further purification.

Reference： [1]Patent: WO2013/24082,2013,A1 .Location in patent: Page/Page column 85

66
[ 2181-42-2 ]
[ 1436-34-6 ]
[ 4938-52-7 ]

Yield	Reaction Conditions	Operation in experiment
90%		To a solution of trimethylsulfonium iodide (8.14 g, 39.94 mmol) in THF (40 mL) at -20 C was added n-BuLi (1.6 M in hexane, 23.7 mL, 37.92 mmol) dropwise and the resulting solution was stirred for 1 h at -20 C. After being stirred for 1 h, a solution of epoxide 2 (1 g, 9.98 mmol) in THF (6 mL) was added. The resultant cloudy suspension was allowed to warm slowly to 25 C over 1 h and stirred for another 1 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with water. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography (5% EtOAc/hexanes) gave 1.030 g (90%) of allylic alcohol 12 as a colourless liquid. +9.3 (c 1.5, CHCl3). IR (KBr); 2923, 2852, 1462, 1219, 772 cm-1; 1H NMR (CDCl3, 300 MHz): delta = 5.81-5.93 (m, 1H), 5.26-5.08 (dd, J = 17.37, 10.57 Hz, 2H), 4.10 (q, J = 6.79 Hz, 1H), 1.59-1.48 (m, 2H), 1.44-1.21 (m, 4H), 0.91 (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3, 75 MHz): delta = 141.2, 114.3, 73.2, 36.6, 27.4, 22.4, 13.8; MS (EI): m/z = 96 [M-H2O]+.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 1397 - 1400
[2]Tetrahedron Asymmetry,2013,vol. 24,p. 594 - 598
[3]European Journal of Organic Chemistry,2013,p. 4586 - 4593

67
[ 124-38-9 ]
[ 2181-42-2 ]
[ 107-02-8 ]
[ 4427-96-7 ]

Yield	Reaction Conditions	Operation in experiment
65%		General procedure: NaH (0.132 g, 3.3 mmol; previously washed with anhydrousPE to remove oil) was taken in an oven-dried three-neckedflask, followed by addition of anhydrous DMSO (10 mL)through a septum to it, and the whole slurry was stirred at 25C under N2 atmosphere. Solid Me3SOI (0.726 g, 3.3 mmol)was added to the slurry with stirring over a period of 5 minvia a solid addition funnel until it becomes a homogeneoussolution. A solution of aldehyde 1a-v (3 mmol), dissolved inanhydrous THF (10 mL), was added dropwise to the reactionmixture. After 1 h, CO2 (1 atm) was then bubbled slowly viaa needle into the reaction mixture, (after ascertaining thataldehyde was completely converted into epoxide, monitoredby TLC) at 40 C, for 6 h. Water (10 mL) was added toquench the reaction. It was then extracted with EtOAc (3 ×20 mL); the organic layer was washed with brine and driedover anhydrous Na2SO4 and the solvent concentrated,product purified by silica gel column chromatography (100-200 mesh) using PE and EtOAc (70:30) as eluent to affordpure cyclic carbonates 4a-v.

Reference： [1]Synlett,2014,vol. 25,p. 97 - 101

68
[ 124-38-9 ]
[ 2181-42-2 ]
[ 104-55-2 ]
(E)-4-styryl-1,3-dioxolan-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
98%		General procedure: NaH (0.132 g, 3.3 mmol; previously washed with anhydrousPE to remove oil) was taken in an oven-dried three-neckedflask, followed by addition of anhydrous DMSO (10 mL)through a septum to it, and the whole slurry was stirred at 25C under N2 atmosphere. Solid Me3SOI (0.726 g, 3.3 mmol)was added to the slurry with stirring over a period of 5 minvia a solid addition funnel until it becomes a homogeneoussolution. A solution of aldehyde 1a-v (3 mmol), dissolved inanhydrous THF (10 mL), was added dropwise to the reactionmixture. After 1 h, CO2 (1 atm) was then bubbled slowly viaa needle into the reaction mixture, (after ascertaining thataldehyde was completely converted into epoxide, monitoredby TLC) at 40 C, for 6 h. Water (10 mL) was added toquench the reaction. It was then extracted with EtOAc (3 ×20 mL); the organic layer was washed with brine and driedover anhydrous Na2SO4 and the solvent concentrated,product purified by silica gel column chromatography (100-200 mesh) using PE and EtOAc (70:30) as eluent to affordpure cyclic carbonates 4a-v.

Reference： [1]Synlett,2014,vol. 25,p. 97 - 101

69
C₁₉H₂₈O [ No CAS ]
[ 2181-42-2 ]
C₂₀H₃₀O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%		Synthesis of compound SA-F To a stirred solution of trimethylsulfonium iodide (6.4 g , 31.5 mmol) in 10 mL of DMSO was added NaH (60%;800 mg , 31.5 mmol). After stirring at room temperature for lh,a suspension of SA-E (870 mg , 3.2 mmol) in 5 mL of DMSO was added drop wise. After 15 h, the reaction mixture was poured into ice-cold water and extracted with 300 mL EtOAc, washed with 100 mL brine solution, dried and evaporated in vacuo, then purified by chromatography (PE:EtOAc = 10: 1) to afford SA-F as a white solid(695 mg, 76% yield).
76%		To a stirred solution of trimethylsulfonium iodide (6.4 g , 31.5 mmol) in 10 mL of DMSO was added NaH (60%;800 mg , 31.5 mmol). After stirring at room temperature for lh,a suspension of SA-E (870 mg , 3.2 mmol) in 5 mL of DMSO was added drop wise. After 15 h, the reaction mixture was poured into ice-cold water and extracted with 300 mL EtOAc, washed with 100 mL brine solution, dried and evaporated in vacuo, then purified by chromatography (PE:EtOAc = 10: 1) to afford SA-F as a white solid(695 mg, 76% yield).
695 mg		Step 5. Synthesis of compound 46. To a stirred solution of trimethylsuifonium iodide (6.4 g, 31.5 mmol) in 10 mE of DMSO was added NaH (60%;800 mg , 31.5 mmol).After stirring at room temperature for ih,a suspension of.A5 (870 mg, 3.2 mmoi) in 5 mL of DMSO was added dropwise. After 15 h, the reaction mixture was poured into ice-cold water and extracted with 300 ml, EtOAc, washed with 100 mL brine solution, dried and evaporated in vacua, then purified bychromatography (PE:EtOAc 10:1) to afford MI and its isomer as a solid (695 mg).

Reference： [1]Patent: WO2014/169831,2014,A1 .Location in patent: Page/Page column 82
[2]Patent: WO2014/169832,2014,A1 .Location in patent: Page/Page column 139
[3]Patent: WO2016/82789,2016,A1 .Location in patent: Page/Page column 78; 79

70
[ 2058-72-2 ]
[ 2181-42-2 ]
[ 1330786-80-5 ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3430 - 3433

71
[ 875003-43-3 ]
[ 2181-42-2 ]
7-fluoro-1-methylspiro[indole-3,2'-oxiran]-2(1H)-one [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 3430 - 3433

72
[ 2181-42-2 ]
[ 71653-64-0 ]
2-(2-(difluoromethoxy)phenyl)oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With tetra-(n-butyl)ammonium iodide; sodium hydroxide; In dichloromethane; water; for 144h;	A mixture of <strong>[71653-64-0]2-(difluoromethoxy)benzaldehyde</strong> (110 g, 639 mmol), tetrabutylammonium iodide (2.360 g, 6.39 mmol) and trimethylsulfonium iodide (156 g, 767 mmol) in DCM (900 ml) and aq. NaOH (50%, 600 ml) was vigoursly stirred for 6days. The reaction mixture was diluted with DCM and water and the layers were separated. The water layer was extracted three times with DCM. The organic layers were combined and washed with water and concentrated in vacuo. The residue was diluted with diethylether, washed with aq. Na2S2O3 (1 M,x 2), water (x 2) and brine, and dried (Na2SO4) to give the title compound as a yellow oil (135.8 g, 96%). 1H NMR (300 MHz,CDC13-d) oe 7.31 (ddd, J 8.0, 6.4, 2.8 Hz, 1H), 7.27 - 7.17 (m, 2H), 7.13 (d, J 8.0 Hz,1H), 6.56 (t, J73.8 Hz, 1H), 4.18 (dd, J 4.1, 2.6 Hz, 1H), 3.17 (dd, J 5.6, 4.2 Hz, 1H),2.72 (dd, J 5.7, 2.6 Hz, 1H).

Reference： [1]Patent: WO2015/86525,2015,A1 .Location in patent: Page/Page column 133; 134

73
[ 13949-93-4 ]
[ 2181-42-2 ]
ethyl 2-(oxiran-2-yl)cyclopropanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0358] Sodium hydride (169 mg, 4.22 mmol, 60% in mineral oil) was added to the solution of trimethylsulfonium iodide (861 mg, 4.22 mmol) in THF (10 mL) and DMSO (10 mL) at 0 C, and the resulting mixture stirred at 0 C for 10 mins, followed by the addition of ethyl 2-formylcyclopropanecarboxylate (500 mg, 3.52 mmol). The reaction was stirred for another 1 h, quenched with aqueous NH4C1 and extracted with petroleum ether (30 mL x 2). The combined organic layers were washed with brine, dried and concentrated to afford the title crude compound as colorless oil, which was used in the next step without further purification. LCMS (ESI) calculated for C8Hi303 [M+H]+: 157, found: 157, 1H NMR (400 MHz, CDC13) delta 4.1 1 (2H, d, J = 7.0 Hz,), 2.99-2.78 (1H, m), 2.78-2.70 (1H, m), 2.58-2.47 (1H, m), 1.69-1.59 (2H, m), 1.30-1.17 (3H, m), 1.1 1-1.04 (1H, m), 0.85 (2H, s).

Reference： [1]Patent: WO2015/95792,2015,A1 .Location in patent: Paragraph 0358

74
[ 1791-26-0 ]
[ 2181-42-2 ]
[ 10431-61-5 ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 13624 - 13631

75
[ 26673-31-4 ]
[ 2181-42-2 ]
6-chloro-3,4-dihydro-2H-spiro [naphthalene-1,2’-oxirane] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium hydroxide; In dimethylsulfoxide-d6; at 20℃; for 48h;	A 2L 4-necked-RBF was charged with 6-chloro-3,4-dihydro-l(2H)- naphthalenone (123 g, 681 mmol), trimethylsulfonium iodide (143 g, 701 mmol), and DMSO (1 100 niL). KOH (76 g, 1362 mmol) (pellets) was added. The suspension was stirred at ambient temperature for 2 days, after which time crude lH NMR showed no remaining starting material. The solution was poured into 800 g of crushed ice, rinsed with MTBE (200 mL), and an additional portion of MTBE (700 mL) was added. The resulting mixture was stirred for 5 min and after partition, the bottom aqueous layer was extracted with MTBE twice (500 mL, 300 mL), and combined with the main MTBE extract. The combined organic stream was washed with brine (2X600 mL) and 330 g of AI2O3 (neutral) was added. The resulting suspension was stirred for 5 min at 22C, filtered, and washed with MTBE (400 mL). The filtrate was concentrated to give the product as a red viscous oil (125 g, 94%).
94%	With potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 48h;	A 2L 4-necked RBF was charged 6-chioro-3,4-dihydro-1(2H)-naphthalenone (123 g, 681 nimol), trimethylsulfonium iodide (143 g, 701 nunol)and DMSO (1100 mL, 8.94 mL/g). Potassium hydroxide (76 g, 1362 mmol)(pellets) was added, The suspension was stirred at ambient temperature for 2 daysafter which time crude ?H NMR showed no remaining starting material. Thesolution was poured into 800 g of crushed ice, rinsed with MTBE (200 mE) and an additional portion of MTBE (700 mE) was added. The resulting mixture was stirred for 5 mm. and after partition the bottom aqueous layer was extracted with MTBE twice (500 niL, 300 mL) and combined with the main MTBE extract. Thecombined organic stream was washed with brine (2X600 mL) and 330 g of Al20s (neutral) was added. The resulting suspension was stirred for 5 mm. at 22 C, filtered and washed with MTBE (400 mL). The filtrate was concentrated to give the title compound as a red viscous oil (125 g , 94%).
94%	With potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 48h;	A 2L 4-necked-RBF was charged with 6-chloro-3,4-dihydro-1(2H)- naphthalenone (123 g, 681 mmol), trimethylsulfonium iodide (143 g, 701 mmol), and DMSO (1100 mL). KOH (76 g, 1362 mmol) (pellets) was added. The suspension was stirred at ambient temperature for 2 days, after which time crude?H NMR showed no remaining starting material. The solution was poured into800 g of crushed ice, rinsed with MTBE (200 mL), and an additional portion of MTBE (700 mL) was added. The resulting mixture was stirred for 5 mm and after partition, the bottom aqueous layer was extracted with MTBE twice (500 mL, 300 mL), and combined with the main MTBE extract. The combined organic streamwas washed with brine (2X600 mL) and 330 g of A1203 (neutral) was added. The resulting suspension was stirred for 5 mm at 22C, filtered, and washed with MTBE (400 mL). The filtrate was concentrated to give the product as a red viscous oil (125 g, 94%).

94%	With potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 48h;	A 2L 4-necked-RBF was charged with 6-chloro-3,4-dihydro-l(2H)-naphthalenone (123 g, 681 mmol), trimethylsulfonium iodide (143 g, 701 mmol), and DMSO (1100 mL). KOH (76 g, 1362 mmol) (pellets) was added. The suspension was stirred at ambient temperature for 2 days, after which time crude 'H NMR showed no remaining starting material. The solution was poured into 800 g of crushed ice, rinsed with MTBE (200 mL), and an additional portion of MTBE (700 mL) was added. The resulting mixture was stirred for 5 min and after partition, the bottom aqueous layer was extracted with MTBE twice (500 mL, 300 mL), and combined with the main MTBE extract. The combined organic stream was washed with brine (2X600 mL) and 330 g of AI2O3 (neutral) was added. The resulting suspension was stirred for 5 min at 22C, filtered, and washed with MTBE (400 mL). The filtrate was concentrated to give the product as a red viscous oil (125 g, 94%).
92%	With potassium hydroxide; In dimethyl sulfoxide; at 25℃; for 24h;	To a solution of 6-chlorotetralin-l-one (10.0 g, 55.3 mmol) in DMSO (100 mL) was added trimethyl sulfonium iodide (12.4 g, 60.9 mmol) and hydroxypotassium (6.21 g, 110 mmol), the mixture was stirred at 25 C for 24 hours. The mixture was added to ice water (500 mL), extracted with MTBE (400 mL X 3), combined the organic phases, washed with brine (500 mL X 2), dried over Na2S04, filtered and concentrated in vacuum to give 6'-chlorospiro[oxirane-2,T- tetralin] (10.0 g, 51.3 mmol, 92% yield).

Reference： [1]Patent: WO2016/33486,2016,A1 .Location in patent: Page/Page column 60; 61
[2]Patent: WO2017/147410,2017,A1 .Location in patent: Page/Page column 54
[3]Patent: WO2018/183418,2018,A1 .Location in patent: Page/Page column 778; 779
[4]Patent: WO2019/173181,2019,A1 .Location in patent: Page/Page column 64
[5]Journal of Medicinal Chemistry,2019
[6]Patent: WO2020/97577,2020,A1 .Location in patent: Paragraph 00432

76
[ 50899-03-1 ]
[ 2181-42-2 ]
2-(4-(ethylsulfonyl)phenyl)oxirane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	[00152] To a solution of <strong>[50899-03-1]4-(ethylsulfonyl)benzaldehyde</strong> (10 g, 50.5 mmol) in DMF (85 mL) at rt was added trimethylsulfonium iodide (11.9 g, 58.1 mmol) followed by potassium hydroxide powder (5.66 g, 101 mmol). The reaction mixture was stirred at rt for 20 min before quenching with H20 (50 mL). The mixture was carefully neutralized with 1 N HC1 solution (55 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic phase was washed with brine, dried over anhydrous Na2S04, and passed through a pad of silica gel (eluting with ethyl acetate). It was concentrated under reduced pressure to afford crude 2-(4- (ethylsulfonyl)phenyl)oxirane as yellow oil, which was used directly for the next step without further purification. LC-MS tR = 1.13 min in 2 min chromatography, MS (ESI) m/z 213.2 [M+H]+.
	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	To a solution of <strong>[50899-03-1]4-(ethylsulfonyl)benzaldehyde</strong> (10 g, 50.5 mmol) in DMF (85 mE) at rt was added trimethylsulfonium iodide (11.9 g, 58.1 mmol) followed by potassium hydroxide powder (5.66 g, 101 mmol). The reaction mixture was stirred at rt for 20 mm before quenching with H20 (50 mE). The mixture was carefully neutralized with 1 N HC1 solution (55 mE) and extracted with ethyl acetate (3x100 mE). The combined organic phase was washed with brine,dried over anhydrous Na2SO4, and passed through a pad of silica gel (eluting with ethyl acetate). It was concentrated under reduced pressure to afford crude 2-(4-(ethylsulfonyl) phenyl)oxirane as yellow oil, which was used directly for the next step without further purification. EC-MS tR=l .13 mm in 2 mm chromatography, MS (ESI) mlz 213.2 [M+H].
	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	j000135J To a solution of <strong>[50899-03-1]4-(ethylsulfonyl)benzaldehyde</strong> (10 g, 50.5 mmol) in DMF (85 mL) at rt was added trimethylsulfonium iodide (11.9 g, 58.1 mmol) followed by potassium hydroxide powder (5.66 g, 1001 mmol). The reaction mixture was stirred at rt for 20 mm before quenching with H20 (50 mL). The mixture was carefully neutralized with 1 N HC1 solution (55 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic phase was washed with brine, dried over anhydrous Na2504, and passed through a pad of silica gel (eluting with ethyl acetate). It was concentrated under reduced pressure to afford crude 2-(4-(ethylsulfonyl)phenyl)oxirane as yellow oil, which was used directly for the next step without further purification. LC-MS tR = 1.13 mm in 2 mm chromatography, MS (ESI) m/z 213.2 [M+H].

	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	[00215] Step 2: 2-(4-(ethylsulfonyl)phenyl)oxirane [00216] To a solution of <strong>[50899-03-1]4-(ethylsulfonyl)benzaldehyde</strong> (10 g, 50.5 mmol) in DMF (85 mL) at rt was added trimethylsulfonium iodide (11.9 g, 58.1 mmol) followed by potassium hydroxide powder (5.66 g, 101 mmol). The reaction mixture was stirred at rt for 20 min before quenching with H20 (50 mL). The mixture was carefully neutralized with 1 N HC1 solution (55 mL) and extracted with EtOAc (3 x 100 mL). The combined organic phase was washed with brine, dried over anhydrous Na2S04, and passed through a pad of silica gel (eluting with EtOAc). It was concentrated under reduced pressure to afford crude 2-(4-(ethylsulfonyl)phenyl)oxirane as yellow oil, which was used directly for the next step without further purification. LC-MS tR = 1.13 min in 2 min chromatography, MS (ESI) m/z 213.2 [M+H]+.
1.1 g	With potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.333333h;	To a solution of <strong>[50899-03-1]4-(ethylsulfonyl)benzaldehyde</strong> (Step 1 intermediate) (1.0 g, 5.04 mmol) in DMF (10 mL) was added trimethylsulfonium iodide (1.18 g, 5.80 mmol) followed by potassium hydroxide powder (560 mg, 10.08 mmol) at RT. The mixture was stirred at RT for 20 min. The mixture was quenched with water and carefully neutralized with 1N HCl. The aqueous mixture was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by a quick filter column to yield 1.1 g of the titled product; APCI-MS (m/z) 211 (M+H)-.

Reference： [1]Patent: WO2016/61160,2016,A1 .Location in patent: Paragraph 00152
[2]Patent: US9481674,2016,B1 .Location in patent: Page/Page column 49; 50
[3]Patent: WO2017/87608,2017,A1 .Location in patent: Paragraph 00133; 00135
[4]Patent: WO2017/132432,2017,A1 .Location in patent: Paragraph 00215-00216
[5]Patent: WO2018/42342,2018,A1 .Location in patent: Page/Page column 54

77
(E)-4-(2-(((tert-butyldimethylsilyl)oxy)methyl)-6,6-dimethylcyclohex-1-en-1-yl)but-3-en-2-one [ No CAS ]
[ 2181-42-2 ]
(E)-tert-butyl((3,3-dimethyl-2-(2-(2-methyloxiran-2-yl)vinyl)cyclohex-1-en-1-yl)methoxy)dimethylsilane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%		To a solution of trimethylsulfonium iodide (458 mg, 2.3 mmol) in DMSO (2 ml) was added THF (2 ml) under argon to yield a finely divided suspension of sulfonium salt. This mixture was then cooled to 0 C and treated with a solution of dimsyl sodium (4.4 M, 0.63 ml, 2.7 mmol). The resulting gray colored suspension was treated with a solution of ketone 27 (500 mg, 1.55 mmol) in THF (0.26 ml). After stirring at 0 C for 1 h, the mixture was warmed to room temperature, quenched by successively adding H2O (10 mL) and n-hexane (30 mL). The organic phase was washed with H2O, dried over anhydrous MgSO4, and concentrated in vacuo to give the epoxide 28 (522 mg, 1.55 mmol, 100%). 1H-NMR (CDCl3, 400 MHz) delta: 0.00 (6H, s, Si-(CH3)2), 0.86 (9H, s, Si-C(CH3)3), 0.959 (3H, s, 3-CH3), 0.961 (3H, s, 3-CH3), 1.40-1.45 (2H, m, H-4), 1.46 (3H, s, 2''-CH3), 1.55-1.60 (2H, m, H-5), 2.07-2.13 (2H, m, H-6), 2.69 (1H, dd, J = 0.5, 5.4 Hz, H-3''), 2.80 (1H, d, J = 5.4 Hz, H-3''), 4.08 (1H, d, J = 11.5 Hz, OCH2), 4.12 (1H, d, J = 11.5 Hz, OCH2), 5.24 (1H, d, J = 16.1 Hz, H-2'), 6.13 (1H, dt, J = 16.5, 1.9 Hz, H-1'); 13C-NMR (CDCl3, 100 MHz) delta: -5.2, 18.4, 19.0, 19.9, 26.0, 27.5, 28.6, 34.0, 39.0, 55.6, 55.9, 64.5, 128.8, 132.7, 134.9, 139.1; EI-MS m/z: 336 [M]+, 321, 305, 279; HREIMS m/z: 336.2504 [M]+ (calcd. for C20H36O2Si, m/z 336.2484).

Reference： [1]Phytochemistry,2016,vol. 130,p. 90 - 98

78
(3E)-4-(3-isopropyldimethylsilyloxy-2,6,6-trimethylcyclohex-1-en-1-yl)but-3-en-2-one [ No CAS ]
[ 2181-42-2 ]
(E)-isopropyldimethyl((2,4,4-trimethyl-3-(2-(2-methyloxiran-2-yl)vinyl)cyclohex-2-en-1-yl)oxy)silane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%		To a solution of trimethylsulfonium iodide (11.1 g, 54.3 mmol) in DMSO (47 mL) was added tetrahydrofuran THF (47 mL) under Ar to yield a finely divided suspension of sulfonium salt. This mixture was then cooled to -5 C and treated with a solution of dimsyl sodium (4.4 M, 13 mL, 57.2 mmol). The resulting gray colored suspension was treated with a solution of isopropyldimethylsilyloxy-beta-ionone 16 (11.2 g, 36.2 mmol) in THF (11.2 mL). After stirring at -5 C for 45 min, the mixture was warmed to room temperature, quenched by successively adding H2O (200 mL) and n-hexane (200 mL). The organic phase was washed with H2O, dried over anhydrous Na2SO4, and concentrated in vacuo to give the epoxide 17 (11.1 g, 36.1 mmol). 1H-NMR (CDCl3, 400 MHz) delta: 0.09 (6H, s, Si-(CH3)2), 0.80-0.90 (1H, m, Si-CH), 0.95 (3H, d, J = 11.0 Hz, Si-CH-CH3), 0.96 (3H, s, 4-CH3), 0.97 (3H, d, J = 7.1 Hz, Si-CH-CH3), 1.02 (3H, s, 4-CH3), 1.34-1.82 (4H, m, H-5 and H-6), 1.49 (3H, s, 2''-CH3), 1.69 (3H, s, 2-CH3), 2.73 (1H, d, J = 5.4 Hz, H-3''), 2.83 (1H, d, J = 5.4 Hz, H-3''), 4.00 (1H, t, J = 5.4 Hz, H-1), 5.28 (1H, d, J = 16.4 Hz, H-2'), 6.15 (1H, d, J = 16.4 Hz, H-1'); 13C-NMR (CDCl3,100 MHz) delta: -3.7, -3.5, 15.0, 17.0 and 17.1, 18.0 and 18.1, 19.69 and 19.74, 28.2, 29.2, 34.4 and 34.5, 35.08 and 35.13, 55.7 and 55.9, 71.0, 129.7, 130.9, 134.9, 135.0, 139.4 and 139.5; MS data was not obtainable due to instability of the compound.

Reference： [1]Phytochemistry,2016,vol. 130,p. 90 - 98

79
[ 4969-01-1 ]
[ 2181-42-2 ]
1,6,9-trioxadispiro[2.1.4.3]dodecane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step 1-Synthesis of 1,6,9-trioxadispiro[2.1.4.3]dodecane To a stirred solution of NaH (60% in mineral oil, 1.62 g, 39.8 mmol) in DMF (50.0 mL) at 0 C., was added Me3S+I- (7.71 g, 37.3 mmol) in one portion and stirred for 45 minutes. A solution of 1, 4-dioxaspiro[4.5]decan-7-one (3.99 g, 25.5 mmol) in DMF (15.0 mL) was added slowly at 0 C. The reaction mixture was warmed to room temperature and stirred for 22 hours. The reaction was quenched with water (50.0 mL), saturated solution of NaHCO3 (200 mL) and extracted with EtOAc (400 mL). The organic layer was washed with brine (400 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide the product (2.87 g, crude) as yellow oil. MS: m/z=171 (M+H+).

Reference： [1]Patent: US2017/217986,2017,A1 .Location in patent: Paragraph 0455; 0456

80
[ 22929-52-8 ]
[ 2181-42-2 ]
[ 185-61-5 ]

Yield	Reaction Conditions	Operation in experiment
1%		Step 1. Synthesis of Intermediate 5-2. To a mixture of trimethylsulfoxonium iodide (28.3 g, 139 mmol) in DMSO (60 mL) was added NaH (5.55 g, 60percent in mineral oil, 139 mmol) in portions at 5 °C under N2 and the mixture was stirred at 5 °C for 30 mins. Dihydrofuran-3(2H)- one (10 g, 116 mmol) in DMSO (40 mL) was added dropwise while maintaining the temperature below 15 °C and the resulting mixture was stirred at 15 °C for 20 hrs. The reaction was quenched at 10 °C with water (200 mL) and extracted with MTBE (2 x 200 mL). The combined organic phases were washed with brine (200 mL), dried over Na2SO4, filtered and concentrated and the residue was purified by silica gel chromatography (0percent~40percent EtOAc in PE) to afford Intermediate 5-2 (100 mg, 1percent) as a colorless oil. (0326) 1H NMR (400 MHz, CDCl3) delta 4.12-3.93 (m, 3H), 3.68 (d, J = 10.4Hz, 1H), 3.05 (d, J = 4.4Hz, 1H), 2.96 (d, J = 4.4Hz, 1H), 2.37-2.25 (m, 1H), 2.02-1.92 (m, 1H).

Reference： [1]Patent: WO2017/173358,2017,A1 .Location in patent: Paragraph 00136

81
[ 359-41-1 ]
[ 67442-07-3 ]
[ 2181-42-2 ]
[ 1388149-59-4 ]

Yield	Reaction Conditions	Operation in experiment
49%		To a solution of trimethylsulfonium iodide (41.51 g, 203.9 mmol) in THF (335.3 mL)at -30 °C was added lithium bis(trimethylsilyl)amide (1M in heptane, 203.9 mL, 203.9mmol) portionwise over 45 mills. After stirring for 30 mins, 3,3,3-trifluoro-1,2- epoxypropane (14 g, 124.9 mmol) was added at -20 °C over 15 mill, and the mixture was allowed to warm to RT and stirred for 3 h and 10 mm. The slurry was then added portionwise to an ice-cold solution of <strong>[67442-07-3]2-chloro-N-methoxy-N-methylacetamide</strong> (28.05g, 203.9 mmol) in NMP (75.7 mL). The resulting mixture was allowed to warm to RT and stirred for 1 day before dilution with EtOAc. The organic layer was washed with NaHCO3 (sat. aq. sol.) and the washings extracted with EtOAc. The organic layers were combined, dried (MgSO4) and evaporated. The residue was purified by column chromatography (silica gel; n-heptane/EtOAc 100/0 to 70/30) to yield 1-1 (13.8 g,49percent).

Reference： [1]Patent: WO2018/83247,2018,A1 .Location in patent: Page/Page column 28

82
[ 78531-45-0 ]
(1S,3’R,6’R,8’E,11’S,12’R)-6-chloro-11’,12'-dimethyl-3,4-dihydro-2H,7’H,15’H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.03,6.019,24]pentacosa[8,16,18,24]tetraene]-7',15'-dione-13',13’-dioxide [ No CAS ]
[ 2181-42-2 ]
(1S,3'R,6'R,7'S,8'E,11'S,12'R)-6-chloro-7'-(cis-5-(dimethylamino)-1,3-dioxan-2-yl)-11',12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0~3,6~0~19,24~]pentacosa[8,16,18,24]tetraen]-15'one 13',13'-dioxide [ No CAS ]
(1S,3'R,6'R,7'R,8'E,11'S,12'R)-6-chloro-7'-(cis-5-(dimethylamino)-1,3-dioxan-2-yl)-11',12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0~3,6~0~19,24~]pentacosa[8,16,18,24]tetraen]-15'one 13',13'-dioxide [ No CAS ]
(1S,3'R,6'R,7'S,8'E,11'S,12'R)-6-chloro-7'-(trans-5-(dimethylamino)-1,3-dioxan-2-yl)-11',12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0~3,6~0~19,24~]pentacosa[8,16,18,24]tetraen]-15'one 13',13'-dioxide [ No CAS ]
(1S,3'R,6'R,7'R,8'E,11'S,12'R)-6-chloro-7'-(trans-5-(dimethylamino)-1,3-dioxan-2-yl)-11',12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-1,22'-[20]oxa[13]thia[1,14]diazatetracyclo[14.7.2.0~3,6~0~19,24~]pentacosa[8,16,18,24]tetraen]-15'one 13',13'-dioxide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a stirred solution of (l S,3'R,6'R,8'E,H'S,12'R)-6-chloro-H',12'- dimethyl-3,4-dihydro-2H,7'H,15'H-spiro[naphthalene-l,22'- [20]oxa[13]thia[l,14]diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,2 4]tetraene]-7',15'-dione 13',13'-dioxide (200 mg, 0.335 mmol) and (0500) trimethylsulfonium iodide (71.8 mg, 0.352 mmol) in dimethyl sulfoxide (2.0 mL) was dropwise added potassium tert-butoxide, 1.0m solution in tetrahydrofuran (0.837 mL, 0.837 mmol) under argon over 5 min. The resulting mixture was stirred at ambient temperature for 15 min. The crude reaction mixture was directly loaded onto a silica gel precolumn previously covered with a layer of ammonium chloride and subjected to combi-flash column chromatography on a 12-g ISCO Gold eluting with EtOAc/Hexanes (15 min from 20 to 100% and 10 min at 100%) to give, as minor products, an impure epimeric mixture of (1 S,3'R,6'R,7'S,8'E, 1 l'S, 12'R)-6-chloro- 1 Gamma, 12'-dimethyl- 15'-oxo-3,4-dihy dro-2H- spiro [naphthalene- 1 ,22'- [20] oxa[ 13] thia[ 1 , 14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraene]-7'-carbaldehyde 13',13'- dioxide and (1 S,3'R,6'R,7'R,8'E, 1 l'S, 12'R)-6-chloro-l 1 ', 12'-dimethyl- 15'-oxo-3,4- dihy dro-2H-spiro [naphthalene- 1 ,22'-[20] oxa[ 13]thia[ 1,14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraene]-7'-carbaldehyde 13',13'- dioxide (50 mg) as a white solid. It was directly taken onto the next step without further purification. MS (ESI, +ve) m/z 611.4 [M + H]+ An impure mixture of (lS,3'R,6'R,7'S,8'E,H'S,12'R)-6-chloro-H',12'-dimethyl- 15 '-oxo-3 ,4-dihy dro-2H-spiro [naphthalene- 1 ,22'- [20] oxa[ 13] thia[ 1 , 14] diazatetracy clo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraene]-7'- carbaldehyde 13 ',13 '-dioxide and (lS,3'R,6'R,7'R,8'E,H'S,12'R)-6-chloro-H',12'- dimethyl-15'-oxo-3,4-dihydro-2H-spiro[naphthalene-l,22'-[20]oxa[13]thia[l,14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraene]-7'- carbaldehyde 13',13'-dioxide (24 mg, 0.039 mmol), 2-(dimethylamino)propane- 1,3-diol (70.2 mg, 0.589 mmol), and 4-methylbenzene sulfonic acid, monohydrate (116 mg, 0.609 mmol) in toluene (40 mL) in a 50-mL round-bottomed flask equipped with a Dean-Stark condenser was heated at reflux for 4 h. Both the precipitate and the toluene layer showed the presence of the desired products although weak in signal. The crude mixture was left at rt overnight before directly loaded in DCM/MeOH onto a silica gel precolumn (25 g) previously covered with a layer of sodium bicarbonate and subjected to combi-fiash column chromatography on a 4-g ISCO GOLD eluting with MeOH/DCM to give two isomeric products: (lS,3'R,6'R,7'S,8'E,ll'S,12'R)-6-chloro-7'-(cis-5- (dimethylamino)-l ,3-dioxan-2-yl)-l Gamma, 12'-dimethyl-3,4-dihydro-2H, 15- spiro [naphthalene- 1 ,22'-[20]oxa[ 13]thia[ 1,14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraen]-15'-one 13',13'-dioxide OR(lS,3'R,6'R,7'R,8'E,irS,12'R)-6-chloro-7'-(cis-5-(dimethylamino)-l,3- dioxan-2-yl)-ir,12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-l,22'- [20]oxa[13]thia[l,14]diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,2 4]tetraen]-15'-one 13',13'-dioxide OR (lS,3'R,6'R,7'S,8'E,ll'S,12'R)-6-chloro-7'- (Trans-5-(dimethylamino)-l,3-dioxan-2-yl)-i ,12'-dimethyl-3,4-dihydro- 2H, 15'H-spiro[naphthalene- 1 ,22'-[20] oxa[l 3]thia[ 1,14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraen]-15'-one 13',13'-dioxide OR(lS,3'R,6'R,7'R,8'E,irS,12'R)-6-chloro-7'-(Trans-5-(dimethylamino)-l,3- dioxan-2-yl)-ir,12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-l,22'-[20]oxa[13]thia[l,14]diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,2 4]tetraen]-15'-one 13',13'-dioxide (Example 97) as an off-white solid. It was the second eluting isomer off of silica gel column. NMR (400 MHz, CHLOROFORM-d) delta 7.70 (d, J=8.61 Hz, 1H), 7.19 (dd, J=2.25, 8.51 Hz, 1H), 7.09 (d, J=2.15 Hz, 1H), 6.84-6.96 (m, 3H), 5.65-5.77 (m, 1H), 5.48-5.58 (m, 1H), 4.39 (br d,J=3.91Hz, 3H), 4.31 (q,J=7.04 Hz, 1H), 4.04-4.11 (m, 2H), 3.83-3.95 (m, 2H), 3.79 (br d, J=15.26 Hz, 1H), 3.70 (br d, J=14.28 Hz, 1H), 3.23 (d, J=14.28 Hz, 1H), 2.91-2.99 (m, 1H), 2.73-2.81 (m, 2H), 2.55-2.69 (m, 6H), 2.38- 2.48 (m, 3H), 1.55-2.12 (m, 9H), 1.48 (d, J=7.24 Hz, 3H), 1.20-1.42 (m, 3H), 1.04 (d, J=6.65 Hz, 3H). MS (ESI, +ve) m/z 71.2. [M + H]+; and (l S,3'R,6'R,7'S,8i rS,12'R)-6-chloro-7'-(cis-5-(dimethylamino)-l,3-dioxan- 2-yl)-i r,12'-dimethyl-3,4-dihydro-2H,15'H-spiro[naphthalene-l,22'- [20]oxa[13]thia[l,14]diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,2 4]tetraen]-15'-one 13',13'-dioxide OR (lS,3'R,6'R,7'R,8'E,i rS,12'R)-6-chloro-7'- (cis-5-(dimethylamino)-l,3-dioxan-2-yl)-i r,12'-dimethyl-3,4-dihydro-2H,15'H- spiro [naphthalene- 1 ,22'-[20]oxa[ 13]thia[ 1,14] diazatetracyclo[14.7.2.0~3,6~.0~19,24~]pentacosa[8,16,18,24]tetraen]-15'-one 13',13'-dioxide OR (lS,3'R,6'R,7'S,8i rS,12'R)-6-chloro-7'-(Trans-5-(dimethylamino)-l,3- dioxan-2-yl)-i r...

Reference： [1]Patent: WO2019/36575,2019,A1 .Location in patent: Page/Page column 96-99

83
[ 635712-99-1 ]
[ 2181-42-2 ]
2-(benzyloxy)-5-(oxiran-2-yl)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A solution trimethylsulfonium iodide (495 mg, 2.43 mg) in DMSO (7.5 mL) was added dropwise to a suspension of NaH (prepared from NaH, 101 mg, 2.53 mmol, 60 % in mineral oil by washing with Et20) in THF (7.5 mL) at 0 C. The mixture was stirred at 0 C for 30 min and a solution of <strong>[635712-99-1]6-benzyloxynicotinaldehyde</strong> (450 mg, 2.11 mmol) in THF (3 mL) was added dropwise. The cooling bath was removed and the mixture was stirred at rt for 1 h and poured onto ice. The mixture was extracted with EtOAc and the combined extracts washed with H2O, brine, dried over MgSCU and concentrated to give a quantitative yield of the sub-title compound that was used in the next step without further purification.

Reference： [1]Patent: WO2019/53427,2019,A1 .Location in patent: Page/Page column 49-50

84
[ 143306-64-3 ]
[ 2181-42-2 ]
tert-butyl 1-oxa-8-azadispiro[2.0.2⁴.4³]decane-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%		To a stirred solution of trimethylsulfonium iodide (919 mg, 4.51 mmol) in dry DMSO (5.0 ml_) at 0 C was added sodium hydride (180 mg, 4.51 mmol) and the reaction mixture was stirred at rt. After 2 h, a solution of te/f-butyl 8-oxo-5-azaspiro[2.5]octane-5-carboxylate (406 mg, 1.80 mmol) (1443) [commercially available] in DMSO (2.5 ml_) was added and the reaction mixture was heated to 50 C. After a further 16 h, the mixture was cooled to rt and quenched with water before being extracted into diethyl ether (x 3). The combined organic phase was washed with brine, dried (MgS04), the solvents were removed in vacuo , and the remaining residue was purified by flash chromatography (0-40% EtOAc in cyclohexane) to give the title compound (209 mg, 48%) as a colourless oil. LCMS (Method B): RT = 0.89 min, m/z = 140 [M-Boc+H]+.

Reference： [1]Patent: WO2019/150119,2019,A1 .Location in patent: Page/Page column 202-203

85
[ 29943-42-8 ]
[ 2181-42-2 ]
[ 185-72-8 ]

Yield	Reaction Conditions	Operation in experiment
	With tert-butoxide; In dimethyl sulfoxide; at 20℃;Inert atmosphere;	To a solution of trimethylsulfonium iodide (3.27 g, 16 mmol) in DMSO (20 mL) under nitrogen atmosphere was added dihydro-2H-pyran-4(3H)-one (1.0 g, 10 mmol). To the mixture was added slowly a solution of tert-butoxide (1.68 g, 15 mmol) in DMSO (15 mL) and the solution was stirred at room temperature overnight. The reaction mixture was diluted slowly with water (50 mL) and extracted with diethylether (3x 20 mL). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure providing crude l,6-dioxaspiro[2.5]octane (650 mg), which was directly used without further purification. NMR (300 MHz, chloroform-d) 6.[ppm]: 1.44 - 1.62 (m, 2 H) 1.76 - 1.98 (m, 2 H) 2.70 (s, 2 H) 3.70 -3.98 (m, 4 H).

Reference： [1]Patent: WO2011/26917,2011,A1 .Location in patent: Page/Page column 65

86
[ 2181-42-2 ]
[ 262268-58-6 ]
(E)-2-(3-(trifluoromethyl)styryl)oxirane [ No CAS ]

Reference： [1]Chemical Communications,2020,vol. 56,p. 2131 - 2134

87
[ 51656-91-8 ]
[ 2181-42-2 ]
(±)-ethyl 7,10-dioxadispiro[2.2.4⁶.2³]dodecane-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		A solution of trimethylsulfonium iodide (193 mg, 0.80 mmol) and potassium tert-butoxide (99 mg, 0.88 mmol) in DMSO (5 mL) was stirred at room temperature for half an hour. The product of Step 1 (60 mg, 0.27 mmol) in DMSO (1 mL) was added. After stirring at room temperature for 2 days, the mixture was quenched with water (50 mL) and extracted with ethyl acetate (20mL x 3). The combined organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration and concentration, the residual was purified by silica gel column chromatography eluted with petroleum ether: ethyl acetate (5:1) to obtain the product as an oil (46 mg, 43%). MS ESI: m/z = 241.1, [M+H]+.

Reference： [1]Patent: EP3753926,2020,A1 .Location in patent: Paragraph 0133; 0136; 0137

88
[ 19099-93-5 ]
[ 2181-42-2 ]
[ 77211-75-7 ]

Yield	Reaction Conditions	Operation in experiment
61%		NaH (60% in mineral oil, 2 g, 50 mmol) was added in portions toa solution of trimethylsulfonium iodide (6.6 g, 30 mmol) in DMSO(100 mL) cooled to 0 C. After complete addition the ice bath wasremoved and the solution was stirred for another 40 min atambient temperature. After addition of 1-(benzyloxycarbonyl)-4-piperidone (4.66 g, 20 mmol), the mixture was heated to 55 Cfor 2 h (TLC: hexane/ethyl acetate, 70/30, Rf 0.38), cooled toambient temperature and poured onto ice. The product was extracted with ethyl acetate, washed with water and dried overNa2SO4. After removing the solvent under reduced pressure, furtherpurificationwas carried out by flash chromatography (hexane/ethylacetate, 70/30). The product 14c-1 (3 g, 61%) was obtained as acolorless oil. 1H NMR (400 MHz, CDCl3) δ 1.50 (dd, J 11.6, 6.7 Hz,2H), 1.74e1.98 (m, 2H), 2,64 (d, J 9.1 Hz, 1H), 3.52 (ddd, J 13.3,9.6, 3.7 Hz, 2H), 3.76e3.98 (m, 2H), 5.18 (d, J 0.6 Hz, 2H),7.27e7.48 (m, 5H). 13C NMR (101 MHz, CDCl3) δ 32.9, 39.5, 42.7,49.5, 53.7, 56.9, 65.2, 67.2, 73.2, 126.9, 127.5, 127.6, 127.8, 127.9, 128,128.1, 128.4, 128.5, 136.7, 138.1,. 141.2, 155.2. C14H17NO3 HRMS m/z:[MH] Calcd 248.1281; Found 248.1280.

Reference： [1]European Journal of Medicinal Chemistry,2021,vol. 214

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	2181-42-2	MDL No. :	MFCD00011632
Formula :	C₃H₉IS	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VFJYIHQDILEQNR-UHFFFAOYSA-M
M.W :	204.07	Pubchem ID :	75127
Synonyms :

Num. heavy atoms :	5
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 :	38.98
TPSA :	25.3 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.3 cm/s

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.75
Log Po/w (WLOGP) :	-2.5
Log Po/w (MLOGP) :	2.23
Log Po/w (SILICOS-IT) :	-0.71
Consensus Log Po/w :	0.15

[ CAS No. 2181-42-2 ] {[proInfo.proName]}

Quality Control of [ 2181-42-2 ]

Related Doc. of [ 2181-42-2 ]

Product Details of [ 2181-42-2 ]

Calculated chemistry of [ 2181-42-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 2181-42-2 ]

Application In Synthesis of [ 2181-42-2 ]

[ 2181-42-2 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-2.21
Solubility :	1.26 mg/ml ; 0.0062 mol/l
Class :	Soluble
Log S (Ali) :	-1.9
Solubility :	2.58 mg/ml ; 0.0126 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.03
Solubility :	19.1 mg/ml ; 0.0935 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.46

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P301+P312-P302+P352-P304+P340-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P378
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P391	Collect spillage. Hazardous to the aquatic environment
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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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.
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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.
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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:
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