反应详情

To a stirred and refluxing Grignard-complex previously prepared starting from 14.6 parts of magnesium and 105 parts of 1-bromo-4-fluorobenzene in 450 parts of 1,1'-oxybisethane, was added dropwise a solution of 94 parts of 4-phenyl-1-(phenylmethyl)-4-piperidinecarbonitrile monohydrochloride in 360 parts of methylbenzene. About 250 parts of 1,1'-oxybisethane were distilled off at an internal temperature of 60°-65° C. The turbid solution was stirred and refluxed for 5 hours. The reaction mixture was decomposed with a saturate ammonium chloride solution in water. The layers were separated and the organic phase was dried, filtered and evaporated. The oily residue was boiled in a dilute hydrochloric acid solution. After cooling, the whole was alkalized with ammonium hydroxide and extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane, yielding 91 parts (81%) of (4-fluorophenyl) [4-phenyl-1-(phenylmethyl)-4-piperidinyl]methanone; mp. 147.6° C. (intermediate 13).

1. temperaturerefluxing Grignard-complex
2. custompreviously prepared
3. distillationAbout 250 parts of 1,1'-oxybisethane were distilled off at an internal temperature of 60°-65° C
4. stirringThe turbid solution was stirred
5. temperaturerefluxed for 5 hours
6. customThe layers were separated
7. customthe organic phase was dried
8. filtrationfiltered
9. customevaporated
10. temperatureAfter cooling
11. extractionextracted with trichloromethane
12. customThe extract was dried
13. filtrationfiltered
14. customevaporated
15. customThe residue was crystallized from a mixture of 2-propanol and 2,2'-oxybispropane