反応 #43469

反応方程式

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

溶媒

THF

DMF

反応条件

後処理

1. 1
   その他the ice-water bath was removed
2. 2
   workup.WAITthe stirring was continued between 0° C. to RT for 2 hr before it
3. 3
   その他was quenched with saturated NH4Cl solution
4. 4
   workup.ADDITIONThe mixture was diluted with EtOAc, organic layer
5. 5
   その他was separated
6. 6
   洗浄washed with water
7. 7
   乾燥dried over MgSO4
8. 8
   濃縮concentrated
9. 9
   その他Purification by silica gel chromatography (30-100% EtOAc in hexanes)

実験手順

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]+.

出典