反应详情

温度

35 °C

To a mixture of 2.4-dibromo-3-(difluoromethoxy) benzoic acid (10 g) and thionyl chloride (4.38 gm) was added a mixture of toluene (15 ml) and N,N-dimethyl formamide (0.2 ml). The reaction mixture was heated slowly to reflux and stirred at reflux for about 2.5 hours. The reaction mixture was then cooled to 35° C. and added a solution of ethyl 3,3-dimethylaminoacrylate (4.13 gm), and triethylamine (3.79 gm) in toluene (20 ml) drop-wise during a period of about 1 hour maintaining a temperature of 35-40° C. After the addition was over, the reaction temperature was slowly increased to 60-65° C. and stirred the reaction mixture for about 24 hours. Cooled the reaction mixture to 30° C., added water (20 ml) and stirred for about 10 minutes. The organic layer was separated, cooled to about 5° C. and cyclopropylamine (1.82 gm) was added to it drop-wise maintaining temperature at 8-10° C. during a period of about 10 minutes. Stirred the reaction mixture for about 2 hours, solvent was removed under vacuum (˜80% of the original amount) and cooled the reaction mixture to about 20° C. The solid separated was filtered and dried to afford ethyl 3-cyclopropylamino-2-[2,4-dibromo-3(difluoromethoxy) benzoyl]-2-propenoate (10 gm).

1. additionwas added
2. temperatureThe reaction mixture was heated slowly
3. temperatureto reflux
4. temperatureat reflux for about 2.5 hours
5. temperaturemaintaining a temperature of 35-40° C
6. additionAfter the addition
7. temperaturewas slowly increased to 60-65° C.
8. stirringstirred the reaction mixture for about 24 hours
9. temperatureCooled the reaction mixture to 30° C.
10. stirringstirred for about 10 minutes
11. customThe organic layer was separated
12. temperaturecooled to about 5° C.
13. additioncyclopropylamine (1.82 gm) was added to it
14. temperaturedrop-wise maintaining temperature at 8-10° C. during a period of about 10 minutes
15. stirringStirred the reaction mixture for about 2 hours
16. customsolvent was removed under vacuum (˜80% of the original amount) and
17. temperaturecooled the reaction mixture to about 20° C
18. customThe solid separated
19. filtrationwas filtered
20. customdried