反应详情

温度

0 °C

To a stirred and refluxing Grignard complex previously prepared starting from 80.2 parts of 4-chloro-1-methylpiperidine, 14.6 parts of magnesium and 270 parts of tetrahydrofuran, was added dropwise a solution of 101 parts of (2-fluorophenyl)phenylmethanone in 450 parts of tetrahydrofuran. Upon completion, stirring was continued for 18 hours at reflux temperature. The reaction mixture was cooled in an ice-bath and decomposed with a solution of 32 parts of ammonium chloride in 160 parts of water. After stirring for 30 minutes, the product was filtered off and washed with tetrahydrofuran. The filtrate was evaporated, the residue was taken up in methylbenzene and the latter was evaporated again in a boiling water-bath. The residue was dissolved in 700 parts of 2,2'-oxybispropane. The turbid solution was filtered and gaseous hydrogen chloride was bubbled through the filtrate. The solid product was filtered off and suspended in 1000 parts of water. The suspension was treated with ammonium hydroxide and extracted twice with 280 parts of 1,1'-oxybisethane. The combined extracts were dried, filtered and evaporated. The oily residue was crystallized from 240 parts of acetonitrile. After cooling to 0° C., the product was filtered off and dried, yielding 66 parts (44%) of α-(2-fluorophenyl)-1-methyl-α-phenyl-4-piperidinemethanol (intermediate 33).

1. temperaturerefluxing Grignard complex
2. custompreviously prepared
3. stirringUpon completion, stirring
4. temperatureat reflux temperature
5. temperatureThe reaction mixture was cooled in an ice-bath
6. stirringAfter stirring for 30 minutes
7. filtrationthe product was filtered off
8. washwashed with tetrahydrofuran
9. customThe filtrate was evaporated
10. customthe latter was evaporated again in a boiling water-bath
11. dissolutionThe residue was dissolved in 700 parts of 2,2'-oxybispropane
12. filtrationThe turbid solution was filtered
13. customgaseous hydrogen chloride was bubbled through the filtrate
14. filtrationThe solid product was filtered off
15. additionThe suspension was treated with ammonium hydroxide
16. extractionextracted twice with 280 parts of 1,1'-oxybisethane
17. customThe combined extracts were dried
18. filtrationfiltered
19. customevaporated
20. customThe oily residue was crystallized from 240 parts of acetonitrile
21. filtrationthe product was filtered off
22. customdried