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 1478726Notes

Reaction equation

HRID 1478726 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

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+].

Workup

  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

Sources & evidence

ORD record
ord-c539bc3b0c35412a81f5f7604316af73
Source dataset
uspto-grants-2016_08
Patent number
US09403846B2

Reaction notes

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