Sodium hydride → N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(oxiran-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

HRID 1478726노트

반응식

HRID 1478726 반응식
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C@:17]12[CH2:26][O:25][C@@H:24]([CH:27]=[O:28])[CH2:23][C@H:22]1[CH2:21][S:20][C:19]([NH:29][C:30](=[O:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[N:18]2.[Cl-].[NH4+]>CS(C)=O.ClCCl>[F:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[CH:12][C:11]=1[C@:17]12[CH2:26][O:25][C@@H:24]([CH:27]3[CH2:4][O:28]3)[CH2:23][C@H:22]1[CH2:21][S:20][C:19]([NH:29][C:30](=[O:37])[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)=[N:18]2

참가 물질

7

반응물 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 89889275N-[(4aR,6R,8aS)-8a-(2,4-Difluorophenyl)-6-formyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

생성물 1

HCID 90253555N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-(oxiran-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매2회HCID 6344Dichloromethane용매

실험 절차

Sodium hydride (60% in mineral oil, 295 mg, 7.38 mmol) was added to a solution of trimethylsulfoxonium iodide (97%, 1.83 g, 8.07 mmol) in dimethyl sulfoxide (15 mL). After 30 minutes, the mixture was cooled in an ice bath, and a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluorophenyl)-6-formyl-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (P1) (1.12 g, 2.69 mmol) in dimethyl sulfoxide (5 mL) was added. The reaction mixture was allowed to warm to room temperature and stir for 2 hours, at which time saturated aqueous ammonium chloride solution was added, followed by dichloromethane, and the mixture was washed twice with water and with saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo. The product was obtained as a white foamy solid, estimated to be a roughly 4:3 mixture of diastereomers by LCMS analysis; this material was used without additional purification. Yield: 1.19 g, quantitative. LCMS m/z 431.1 [M+H+].

후처리

  1. temperaturethe mixture was cooled in an ice bath
  2. additionwas added
  3. washthe mixture was washed twice with water and with saturated aqueous sodium chloride solution
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe product was obtained as a white foamy solid
  8. additiona roughly 4:3 mixture of diastereomers by LCMS analysis
  9. customthis material was used without additional purification

출처 및 근거

ORD 기록
ord-c539bc3b0c35412a81f5f7604316af73
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09403846B2

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