反应详情

To a stirred and hot (60°-70° C.) mixture of 36 g of 4-methyl-1-(phenylmethyl)-4-piperidinol and 15 ml of acetonitrile were added dropwise 55 ml of concentrated sulfuric acid while cooling. After complete addition, stirring was continued for 20 hours at room temperature. The reaction mixture was poured on crushed ice. The whole was neutralized with potassium carbonate and then strongly alkalinized with a potassium hydroxide solution 15%. The free base was extracted with ethyl acetate. The aqueous phase was saturated with potassium hydroxide and extracted again with ethyl acetate. The combined extracts were dried, filtered and evaporated The semi-solid residue was triturated in 1,1'-oxybisethane and filtered. To the filtrate was added 2-propanone until a clear solution was obtained. Then gaseous hydrogen chloride was introduced into it. The precipitated solid salt was filtered off and recrystallized from 2-propanol, yielding 21.5 g of N-[1-(phenylmethyl)-4-methyl-4-piperidinyl]acetamide hydrochloride; mp. 288°-289° C. (interm. 4).

1. temperaturewhile cooling
2. additionAfter complete addition
3. stirringstirring
4. additionThe reaction mixture was poured
5. customon crushed ice
6. extractionThe free base was extracted with ethyl acetate
7. extractionextracted again with ethyl acetate
8. customThe combined extracts were dried
9. filtrationfiltered
10. customevaporated The semi-solid residue
11. customwas triturated in 1,1'-oxybisethane
12. filtrationfiltered
13. additionTo the filtrate was added 2-propanone until a clear solution
14. customwas obtained
15. filtrationThe precipitated solid salt was filtered off
16. customrecrystallized from 2-propanol