反应详情

A mixture of 40 parts of 7-[4,4-bis(4-fluorophenyl)butyl]hexahydro-2-(2-hydroxyethyl)-3,3-dimethylimidazo[1,5-a]pyrazin-1(5H)-one, 19 parts of hydrochloric acid solution 10.5N and 400 parts of water was stirred for one hour in a boiling water-bath on a Rotavapor. After cooling, the reaction mixture was washed twice with 140 parts of 1,1'-oxybisethane. The aqueous phase was alkalized with ammonium hydroxide. The product was extracted twice with 140 parts of 1,1'-oxybisethane. The combined extracts were dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using first a mixture of trichloromethane and methanol (90:10 by volume) and then a mixture of trichloromethane and methanol saturated with ammonia (90:10 by volume) as eluents. The pure fractions were collected and the eluent was evaporated, yielding 33.7 parts (100%) of 4-[4,4-bis(4-fluorophenyl)butyl]-N-(2-hydroxyethyl)-2-piperazinecarboxamide (intermediate 95).

1. temperatureAfter cooling
2. washthe reaction mixture was washed twice with 140 parts of 1,1'-oxybisethane
3. extractionThe product was extracted twice with 140 parts of 1,1'-oxybisethane
4. customThe combined extracts were dried
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified by column-chromatography over silica gel using first
8. additiona mixture of trichloromethane and methanol (90:10 by volume)
9. additiona mixture of trichloromethane and methanol saturated with ammonia (90:10 by volume) as eluents
10. customThe pure fractions were collected
11. customthe eluent was evaporated