Sodium hydride → 1-(3-Chloro-4-cyano-2-methylbenzyl)-2-oxo-octahydrocyclopenta[b]-pyrrol-4-yl benzoate

HRID 642750

Reaction equation

HRID 642750 reaction equation
[C:1]([O:9][CH:10]1[CH:17]2[CH:13]([C:14](=[O:18])[NH:15][CH2:16]2)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC1C2C(NC(=O)C2)CC1)(=O)C1C=CC=CC=1.[H-].[Na+].Br[CH2:40][C:41]1[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[C:43]([Cl:49])[C:42]=1[CH3:50]>C1COCC1.CN(C=O)C>[C:1]([O:9][CH:10]1[CH:17]2[CH:16]([N:15]([CH2:40][C:41]3[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[C:43]([Cl:49])[C:42]=3[CH3:50])[C:14](=[O:18])[CH2:13]2)[CH2:12][CH2:11]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 592595601-Oxo-octahydrocyclopenta[c]pyrrol-4-yl benzoateHCID 592595712-Oxo-octahydrocyclopenta[b]pyrrol-4-yl benzoateHCID 685774134-(Bromomethyl)-2-chloro-3-methylbenzonitrile

Product 1

HCID 592595681-(3-Chloro-4-cyano-2-methylbenzyl)-2-oxo-octahydrocyclopenta[b]-pyrrol-4-yl benzoate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution containing mixtures of compound 1I and 1J (170 mg, 0.69 mmol, different batch than previous lot in example 1) in anhydrous THF (4 mL) and anhydrous DMF (4 mL) was added sodium hydride (27.7 mg, 0.69 mmol) at 0° C., and stirred at 0° C. for 45 min. Compound 7C (169 mg, 0.69 mmol) was added at 0° C., the ice-water bath was removed, and the stirring was continued between 0° C. to RT for 2 hr before it was quenched with saturated NH4Cl solution. The mixture was diluted with EtOAc, organic layer was separated, washed with water, dried over MgSO4, and concentrated. Purification by silica gel chromatography (30-100% EtOAc in hexanes) provide the title compound 7D (90 mg) and 7E (151 mg). Compound 7D: (ES) m/z 409 [M+H]+. Compound 7E: (ES) m/z 409 [M+H]+.

Workup

  1. customthe ice-water bath was removed
  2. waitthe stirring was continued between 0° C. to RT for 2 hr before it
  3. customwas quenched with saturated NH4Cl solution
  4. additionThe mixture was diluted with EtOAc, organic layer
  5. customwas separated
  6. washwashed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (30-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b5af524b9b9e4377bc526f9bbd2dd217
Source dataset
uspto-grants-2010_04
Patent number
US07696241B2

Linked notes

Loading…