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

HRID 877228Notes

Reaction equation

HRID 877228 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

5

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 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.

Workup

  1. stirringThe reaction mixture was stirred for a further 4 h
  2. extractionthe mixture was extracted twice with dichloromethane
  3. washThe combined organic phases were washed with saturated sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. additionThe crude product was treated with diethyl ether in an ultrasonic bath
  7. customthe solid was isolated by filtration

Sources & evidence

ORD record
ord-b5c5c53adc0b46fd84cb6634b717ce14
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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