反应详情

A mixture of thionyl chloride (465 ml) and 2-(3-trifluoromethylphenoxy)nicotinic acid [930 L g; described by F. J. Villani et al, J. Med. Chem. 18, 1 (1975)] was allowed to stand at ambient temperature for 18 hours and was then heated at reflux for 1 hour. Toluene (1 liter) was then added and the solution was evaporated under reduced pressure. The residue thus obtained was dissolved in methylene chloride (3 liters) and treated, with stirring, with triethylamine (453 ml) at ambient temperature. 2,4-Difluoroaniline (422 g) was then added over 1 hour while maintaining the temperature at 10° to 15° C. and the mixture was then heated at reflux for 2 hours. The methylene chloride was removed by distillation and the residue was treated with water (4 liters). A solid of spongy texture was obtained which was filtered off, dried at 50° C. and recrystallised from a mixture of toluene and hexane (2:3; 15 liters), to give N-(2,4-difluorophenyl)-2-(3-trifluoromethylphenoxy)nicotinamide (720 g), m.p. 160°-161° C. as a colourless crystalline solid.

1. temperaturewas then heated
2. temperatureat reflux for 1 hour
3. customthe solution was evaporated under reduced pressure
4. customThe residue thus obtained
5. additiontreated
6. temperaturewhile maintaining the temperature at 10° to 15° C.
7. temperaturethe mixture was then heated
8. temperatureat reflux for 2 hours
9. customThe methylene chloride was removed by distillation
10. additionthe residue was treated with water (4 liters)
11. customA solid of spongy texture was obtained which
12. filtrationwas filtered off
13. customdried at 50° C.
14. customrecrystallised from a mixture of toluene and hexane (2:3; 15 liters)