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

Reaction equation

[H-].[Na+].Br[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:7][CH:6]=1.O.[CH3:25][N:26]([CH:28]=[O:29])C>>[CH:19]1([CH:11]([C:8]2[CH:9]=[CH:10][C:5]([CH2:4][N:26]3[CH2:25][C:10]4[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=4)[C:28]3=[O:29])=[CH:6][CH:7]=2)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

Reactant 4

HCID 962Water

HCID 6228Dimethylformamide

HCID 24758Sodium hydride

HCID 15225592tert-Butyl 2-(4-(bromomethyl)phenyl)-2-cyclopentylacetate

Product 1

HCID 58074501tert-butyl(+)-cyclopentyl{4-[(1-oxo-1,3-dihydro-2H-isoindol-2-yl)methyl]phenyl}-ethanoate

Procedure

At 0° C., 611.3 mg (15.3 mmol, 60% pure) of sodium hydride were added to 2.035 g (15.3 mmol) of 1-oxoindoline in 12 ml of DMF. The mixture was stirred for 30 min, and 6.0 g (12.7 mmol) of tert-butyl(+/−)-[4-(bromomethyl)phenyl](cyclopentyl)acetate were then added at 0° C. The reaction mixture was stirred for a further 4 h, water was then added and the mixture was extracted twice with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The crude product was treated with diethyl ether in an ultrasonic bath and the solid was isolated by filtration. This gave 3.40 g (60.2% of theory) of the target compound.