반응 #43469

반응 방정식

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

용매

THF

DMF

반응 조건

후처리

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

실험 절차

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]+.

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