反应详情

A mixture of 5.04 parts of 4-[5,5-bis(4-fluorophenyl)pentyl]-2-piperazinecarboxamide, 2.9 parts of 2-chloro-N-(5-fluoro-2-methylphenyl) acetamide, 2.1 parts of sodium carbonate, 0.1 parts of potassium iodide and 120 parts of 4-methyl-2-pentanone was stirred and refluxed for 18 hours. After cooling, the reaction mixture was washed with water. The organic layer was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in acetonitrile and 2-propanol. The precipitate was filtered off and the filtrate was evaporated. The residue was dried at 80° C., yielding 5.48 parts (71%) of 2-(aminocarbonyl)-4-[5,5-bis(4-fluorophenyl)pentyl]-N-(5-fluoro-2-methylphenyl)-1-piperazineacetamide monohydrochloride; mp. 148.2° C. (compound 9).

1. temperaturerefluxed for 18 hours
2. temperatureAfter cooling
3. washthe reaction mixture was washed with water
4. customThe organic layer was dried
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified by column chromatography over silica gel using
8. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
9. customThe pure fractions were collected
10. customthe eluent was evaporated
11. filtrationThe precipitate was filtered off
12. customthe filtrate was evaporated
13. customThe residue was dried at 80° C.