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

HRID 877245Notes

Reaction equation

HRID 877245 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:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:18][CH:17]=1.O>CN(C=O)C.C(OCC)(=O)C>[CH:30]1([CH:22]([C:19]2[CH:20]=[CH:21][C:16]([CH2:15][N:5]3[CH2:4][C:3]4[C:7](=[CH:8][CH:9]=[CH:10][C:2]=4[F:1])[C:6]3=[O:11])=[CH:17][CH:18]=2)[C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 15225592tert-Butyl 2-(4-(bromomethyl)phenyl)-2-cyclopentylacetateHCID 220646804-fluoro-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 58136532tert-Butyl(+/-)-cyclopentyl{4-[(4-fluoro-1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-phenyl}acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 0° C., 280 mg (1.85 mmol) of 4-fluoro-2,3-dihydro-1H-isoindol-1-one were added to a suspension of 96.3 mg (2.41 mmol, 60% pure) of sodium hydride in 1 ml of DMF. The mixture was stirred for 30 min, and 654.5 mg (1.85 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate were then added at 0° C. Stirring was continued for a further 2 h, and water and ethyl acetate were then added to the reaction mixture. 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 6:1 to 5:1). This gave 394 mg (50.2% of theory) of the target compound.

Workup

  1. stirringStirring
  2. waitwas continued for a further 2 h
  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 6:1 to 5:1)

Sources & evidence

ORD record
ord-05d27f7765fb473687a9154853034bf8
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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