Dimethylformamide → 6-Chloro-2-[3-(2,2,2-trifluoroethoxy)pyridin-4-yl]-5-(trifluoromethyl)benzoxazole

HRID 1913666Notes

Reaction equation

HRID 1913666 reaction equation
[H-].[Na+].CN(C=O)C.[F:8][C:9]([F:13])([F:12])[CH2:10][OH:11].[Cl:14][C:15]1[C:30]([C:31]([F:34])([F:33])[F:32])=[CH:29][C:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][C:23]=3F)[O:21][C:17]=2[CH:16]=1>O>[Cl:14][C:15]1[C:30]([C:31]([F:34])([F:32])[F:33])=[CH:29][C:18]2[N:19]=[C:20]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][C:23]=3[O:11][CH2:10][C:9]([F:13])([F:12])[F:8])[O:21][C:17]=2[CH:16]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 668801106-Chloro-2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole

Product 1

HCID 866510576-Chloro-2-[3-(2,2,2-trifluoroethoxy)pyridin-4-yl]-5-(trifluoromethyl)benzoxazoleYield 74.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 46 mg of 60% sodium hydride (in oil) and 2 ml of DMF was stirred at room temperature, to which a mixture solution of 0.12 g of 2,2,2-trifluoroethanol and 0.5 ml of DMF was added. After 15 minutes, 0.28 g of 6-chloro-2-(3-fluoropyridin-4-yl)-5-(trifluoromethyl)benzoxazole was added and stirred at room temperature for one hour. Water was added to the reaction mixture, followed by extraction with ethyl acetate twice. The combined organic layers were washed with a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 0.26 g of 6-chloro-2-[3-(2,2,2-trifluoroethoxy)pyridin-4-yl]-5-(trifluoromethyl)benzoxazole (hereinafter, referred to as “active compound 92”).

Workup

  1. additionwas added
  2. extractionfollowed by extraction with ethyl acetate twice
  3. washThe combined organic layers were washed with a saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-71da608216ea47b7b03eb132b7a08fc5
Source dataset
uspto-grants-2013_12
Patent number
US08609705B2

Reaction notes

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