Reacción #43469

Ecuación de reacción

sodium hydride

compound 1I

1-Oxo-octahydrocyclopenta[c]pyrrol-4-yl benzoate

1J

2-Chloro-4-((3aR,4R,6aS)-4-hydroxy-1-oxo-hexahydrocyclopenta[c]pyrrol-2(1H)-yl)-3-methylbenzonitrile

Compound 7C

4-(Bromomethyl)-2-chloro-3-methylbenzonitrile

→

title compound 7D

2-(3-Chloro-4-cyano-2-methylbenzyl)-1-oxo-octahydrocyclopenta[c]-pyrrol-4-yl benzoate

7E

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

Disolventes

THF

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe ice-water bath was removed
2. 2
   workup.WAITthe stirring was continued between 0° C. to RT for 2 hr before it
3. 3
   Otrowas quenched with saturated NH4Cl solution
4. 4
   workup.ADDITIONThe mixture was diluted with EtOAc, organic layer
5. 5
   Otrowas separated
6. 6
   Lavadowashed with water
7. 7
   Secadodried over MgSO4
8. 8
   Concentraciónconcentrated
9. 9
   OtroPurification by silica gel chromatography (30-100% EtOAc in hexanes)

Procedimiento

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]+.

Fuente