反应详情

温度

60 °C

A mixture of 4.7 parts of 1-(3-chloropropoxy)-4-fluorobenzene, 3.015 parts of cis-4-amino-5-chloro-2-methoxy-N-(3-methoxy-4-piperidinyl)benzamide, 0.1 parts of potassium iodide, 3 parts of N,N-diethylethanamine and 45 parts of N,N-dimethylformiade was stirred and heated for 18 hours at 60° C. The reaction mixture was poured onto water. The precipitated product was filtered off and dissolved in trichloromethane. The solution was washed with water. The organic phase was separated, dried, filtered and evaporated. The residue was purified by column-chromatography over silica gel using a mixture of trichloromethane and methanol (90:10 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The oily residue was crystallized from 2-propanol. The product was filtered off and dried, yielding 3.11 parts (42.8%) of cis-4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxybenzamide monohydrate; mp. 109.8° C. (compound 1).

1. additionThe reaction mixture was poured onto water
2. filtrationThe precipitated product was filtered off
3. dissolutiondissolved in trichloromethane
4. washThe solution was washed with water
5. customThe organic phase was separated
6. customdried
7. filtrationfiltered
8. customevaporated
9. customThe residue was purified by column-chromatography over silica gel using
10. additiona mixture of trichloromethane and methanol (90:10 by volume) as eluent
11. customThe pure fractions were collected
12. customthe eluent was evaporated
13. customThe oily residue was crystallized from 2-propanol
14. filtrationThe product was filtered off
15. customdried