反应详情

A mixture of dimethyl sulfate (0.56 mL, 5.9 mmol) and (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 1.82 g, 6.0 mmol) in 1 M NaOH (25 mL) was heated at 45 degrees for 4.5 h, then a further portion of dimethyl sulfate (0.56 mL, 5.9 mmol) was added and the reaction was heated at 45 degrees overnight. NaOH was added and the mixture was extracted twice with ethyl acetate. The combined organic layers were evaporated and purified by column chromatography, eluting with 10-50% ethyl acetate/dichloromethane followed by recrystallization from ethyl acetate/hexanes to give (4S,7R)-2-(2,4-difluoro-phenyl)-1,7,8,8-tetramethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (199 mg, 11%) as a white solid. ES(+)-MS (M+H) 319.

1. temperaturewas heated at 45 degrees for 4.5 h
2. temperaturethe reaction was heated at 45 degrees overnight
3. extractionthe mixture was extracted twice with ethyl acetate
4. customThe combined organic layers were evaporated
5. custompurified by column chromatography
6. washeluting with 10-50% ethyl acetate/dichloromethane
7. customfollowed by recrystallization from ethyl acetate/hexanes