Water → tert-butyl(+/-)-cyclopentyl{4-[(5,6-difluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}acetate

HRID 877240Notes

Reaction equation

HRID 877240 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=[O:12])[NH:6][CH2:5]2.[H-].[Na+].Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([CH:31]2[CH2:35][CH2:34][CH2:33][CH2:32]2)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:19][CH:18]=1.O>CN(C=O)C.C(OCC)(=O)C>[CH:31]1([CH:23]([C:20]2[CH:21]=[CH:22][C:17]([CH2:16][N:6]3[CH2:5][C:4]4[C:8](=[CH:9][C:10]([F:11])=[C:2]([F:1])[CH:3]=4)[C:7]3=[O:12])=[CH:18][CH:19]=2)[C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 15225592tert-Butyl 2-(4-(bromomethyl)phenyl)-2-cyclopentylacetateHCID 213653915,6-Difluoro-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 58136606tert-butyl(+/-)-cyclopentyl{4-[(5,6-difluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 0° C., 60 mg (0.355 mmol) of 5,6-difluoro-2,3-dihydro-1H-isoindol-1-one were added to 21.3 mg (0.53 mmol, 60% pure) of sodium hydride in 1 ml of DMF. The mixture was stirred for 30 min, and 125.3 mg (0.35 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate 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 10:1 to 2:1). This gave 30.0 mg (19.2% 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 10:1 to 2:1)

Sources & evidence

ORD record
ord-3d83c711a53744f0b0e9ec1d07b2942f
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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