反应详情

温度

0 °C

To a solution of (3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one (98 mg, 0.227 mmol) in DMF (1.10 mL) was added 60% sodium hydride in mineral oil (27.2 mg, 0.680 mmol) at 0° C. After being stirred at 0° C. for 2 min, (bromomethyl)cyclopropane (47.3 μL, 0.680 mmol) was added. The mixture was stirred at 0° C. for 2 h and then warmed to rt. Then the reaction was stirred at rt overnight. The reaction was quenched (sat aq. NH4Cl), extracted (2×EtOAc) and washed (sat. aq. NaCl solution). The combined organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography on silica gel (10% to 20% EtOAc/Hexanes gradient) provided (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((R)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one as the less polar isomer and the title compound as the more polar stereoisomer.

1. stirringThe mixture was stirred at 0° C. for 2 h
2. temperaturewarmed to rt
3. stirringThen the reaction was stirred at rt overnight
4. customThe reaction was quenched (sat aq. NH4Cl)
5. extractionextracted (2×EtOAc)
6. washwashed (sat. aq. NaCl solution)
7. dry with materialThe combined organic layer was dried (Na2SO4)
8. concentrationconcentrated under reduced pressure
9. customPurification by chromatography on silica gel (10% to 20% EtOAc/Hexanes gradient)