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 1478726ノート

反応式

HRID 1478726 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒2 回HCID 6344Dichloromethane溶媒

実験手順

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+].

後処理

  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

出典と根拠

ORDレコード
ord-c539bc3b0c35412a81f5f7604316af73
出典データセット
uspto-grants-2016_08
特許番号
US09403846B2

反応ノート

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