Water → Ethyl 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoate

HRID 877249Notes

Reaction equation

HRID 877249 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:11].[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.C(OCC)(=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:5]2[CH2:4][C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[F:1])[C:6]2=[O:11])=[CH:21][CH:20]=1)[C:23]([O:25][CH2:26][CH3:27])=[O:24]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 220646804-fluoro-2,3-dihydro-1H-isoindol-1-oneHCID 58136537Ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate

Product 1

HCID 58136724Ethyl 4,4,4-trifluoro-2-{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-3-methylbutanoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 0° C., 645 mg (4.27 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to 170.7 mg (4.27 mmol, 60% pure) of sodium hydride in 4 ml of DMF. The mixture was stirred for 30 min, and 2.11 g (5.98 mmol) of ethyl 2-[4-(bromomethyl)phenyl]-4,4,4-trifluoro-3-methylbutanoate were then added at 0° C. The reaction mixture was stirred for a further 2 h, and water and ethyl acetate were then added. 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 40:1 to 3:1). This gave 856 mg (33.9% of theory) of the target compound.

Workup

  1. stirringThe reaction mixture was stirred for a further 2 h
  2. washThe organic phase was washed with saturated sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 40:1 to 3:1)

Sources & evidence

ORD record
ord-4e556c04bd274c0dba037cfda2dcbac8
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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