2,2,2-Trifluoroethanol → (1R,2R,4R)-4-[2-Chloro-4-(2,2,2-trifluoro-ethoxy)-benzenesulfonyl]-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

HRID 1367530Notes

Reaction equation

HRID 1367530 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].[H-].[Na+].[C:9]([C:11]1([NH:14][C:15]([C@@H:17]2[CH2:21][C@@H:20]([S:22]([C:25]3[CH:30]=[CH:29][C:28](F)=[CH:27][C:26]=3[Cl:32])(=[O:24])=[O:23])[CH2:19][C@H:18]2[C:33]([N:35]2[CH2:38][C:37]([F:40])([F:39])[CH2:36]2)=[O:34])=[O:16])[CH2:13][CH2:12]1)#[N:10]>CN(C)C=O>[C:9]([C:11]1([NH:14][C:15]([C@@H:17]2[CH2:21][C@@H:20]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[CH:27][C:26]=3[Cl:32])(=[O:23])=[O:24])[CH2:19][C@H:18]2[C:33]([N:35]2[CH2:38][C:37]([F:40])([F:39])[CH2:36]2)=[O:34])=[O:16])[CH2:13][CH2:12]1)#[N:10]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 59619273(1R,2R,4R)-4-(2-Chloro-4-fluoro-benzenesulfonyl)-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amide

Product 1

HCID 59619478(1R,2R,4R)-4-[2-Chloro-4-(2,2,2-trifluoro-ethoxy)-benzenesulfonyl]-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amideYield 35.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 2,2,2-trifluoroethanol (0.014 mL, 0.20 mmol) and sodium hydride (dispersion in oil, 55% w/w (9 mg, 20 mmol) in N,N-dimethylformamide (2 mL) was added (1R,2R,4R)-4-(2-Chloro-4-fluoro-benzenesulfonyl)-2-(3,3-difluoro-azetidine-1-carbonyl)-cyclopentanecarboxylic acid (1-cyano-cyclopropyl)-amid (Example 119, 80 mg, 0.16 mmol) at room temperature. The reaction mixture was stirred at 50° C. for 16 h, then was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogenocarbonate. The aqueous layer was extracted with ethyl acetate then the combined organic layers were washed with water and brine then dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol (98:2 v/v) as eluant to afford the title compound (32 mg, 31%) as an off-white gum. MS (EI): 570.0 (M+H)+.

Workup

  1. customwas partitioned between ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washthe combined organic layers were washed with water and brine
  4. dry with materialthen dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol (98:2 v/v) as eluant

Sources & evidence

ORD record
ord-3fd7a8b0da8041f4a40ca8ff85cc76a1
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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