Water → tert-Butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]carbamate

HRID 14395

Reaction equation

HRID 14395 reaction equation
[H-].[Na+].[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][NH:16][C:15](=[S:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH2:13][CH2:12]1.FC(F)(F)S(O[CH2:33][C:34]([F:37])([F:36])[F:35])(=O)=O.O>CN(C)C=O>[F:3][C:4]1[C:9]([F:10])=[CH:8][CH:7]=[CH:6][C:5]=1[C@H:11]1[CH2:17][N:16]([CH2:33][C:34]([F:37])([F:36])[F:35])[C:15](=[S:18])[C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:25])[CH3:24])[CH2:13][CH2:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 59734935tert-Butyl (3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-ylcarbamate

Product 1

HCID 86616756tert-Butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-thioxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]carbamateYield 42.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil; 39 mg, 0.975 mmol) was added to a solution of tert-butyl [(3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-yl]carbamate (202 mg, 0.567 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (141 μL, 1.131 mmol) in N,N-dimethylformamide at −25° C. After 15 min, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water (2×), brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (0% hexanes→30% ethyl acetate/hexanes) gave the title compound (105 mg). MS 439.1 (M+1).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water (2×), brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (0% hexanes→30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f4980ddddd214a9d89aff2788ff114c5
Source dataset
uspto-grants-2010_06
Patent number
US07732438B2

Linked notes

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