反应详情

10 parts of cis-4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide were dissolved in 225 parts of hot trichloromethane. After cooling to room temperature, 3.6 parts of N,N-diethylethanamine were added. Then there was added dropwise a solution of 1.7 parts of acetyl chloride in 30 parts of trichloromethane:exothermic reaction. The whole was stirred and refluxed for 22 hours. After cooling to room temperature, 0.6 parts of acetyl chloride were added and stirring was continued overnight at reflux. Another 0.6 parts of acetyl chloride were added and stirring was continued overnight at reflux. After cooling again to room temperature, there were added successively 0.6 parts of acetyl chloride and a small amount of N,N-dimethyl-4-pyridinamine. Stirring was continued for 22 hours at reflux. The reaction mixture was cooled to room temperature and washed with water. The organic phase was dried, filtered and evaporated. The residue was crystallized twice from acetonitrile, yielding 2.78 parts (25.5%) of cis-4-(acetylamino)-5-chloro-N-[1-[3-(4-fluorophenoxy)-propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide; mp. 175.6° C. (compound 233).

1. customexothermic reaction
2. temperaturerefluxed for 22 hours
3. temperatureAfter cooling to room temperature
4. stirringstirring
5. temperatureat reflux
6. stirringstirring
7. waitwas continued overnight
8. temperatureat reflux
9. temperatureAfter cooling again to room temperature
10. stirringStirring
11. waitwas continued for 22 hours
12. temperatureat reflux
13. temperatureThe reaction mixture was cooled to room temperature
14. washwashed with water
15. customThe organic phase was dried
16. filtrationfiltered
17. customevaporated
18. customThe residue was crystallized twice from acetonitrile