Water → Ethyl 4,4,4-trifluoro-3-methyl-2-(4-{[2-oxo-5-(trifluoromethyl)pyridin-1(2H)-yl]methyl}phenyl)butanoate

HRID 877251Notes

Reaction equation

HRID 877251 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[CH:5][C:6](=[O:9])[NH:7][CH:8]=1.[H-].[Na+].Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]([CH:28]([CH3:33])[C:29]([F:32])([F:31])[F:30])[C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:18][CH:17]=1.O>CN(C=O)C>[F:30][C:29]([F:31])([F:32])[CH:28]([CH3:33])[CH:22]([C:19]1[CH:18]=[CH:17][C:16]([CH2:15][N:7]2[CH:8]=[C:3]([C:2]([F:1])([F:10])[F:11])[CH:4]=[CH:5][C:6]2=[O:9])=[CH:21][CH:20]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 1474432-Hydroxy-5-(trifluoromethyl)pyridineHCID 58136537Ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate

Product 1

HCID 58136589Ethyl 4,4,4-trifluoro-3-methyl-2-(4-{[2-oxo-5-(trifluoromethyl)pyridin-1(2H)-yl]methyl}phenyl)butanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.80 g (11.04 mmol) of 5-(trifluoromethyl)pyridin-2(1H)-one were initially charged in 2.5 ml of DMF, and 0.44 g (11.04 mmol, 60% pure) of sodium hydride was added. The mixture was stirred for 30 min, and 3.0 g (8.49 mmol) of ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate were then added. After a further 2 h at RT, water was added and the reaction mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulfate. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1 to 4:1). This gave 2.89 g (78.2% of theory) of the target compound.

Workup

  1. waitAfter a further 2 h at RT
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. washThe organic phase was washed with saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1 to 4:1)

Sources & evidence

ORD record
ord-56f42e2c4f4d4139808532374dc05b4e
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

Loading…