反应详情

温度

30 °C

Phosphoric acid (270 g) is charged in to a round bottom flask and phosphorous pentoxide (270 g) is added in portions at below 140° C. The reaction mixture temperature is allowed to 110° C. and maintained for 2 hours. 3-(2-(4-Chlorophenoxy)phenyl)-1-methylpyrrolidine-2,4-dione (90 g) is added at 110° C. and maintained for 24 hours. Additional phosphorous pentoxide (3×15 g) is added to the reaction mixture in three portions at 110° C. at the time interval of 24 hours. Finally, the reaction mixture is maintained for 48 hours. The reaction mixture is cooled to 25-35° C., poured in to water (4500 mL), and stirred for 15 hours. The reaction mass is extracted with dichloromethane (900 mL), the layers are separated, and the aqueous layer is washed with dichloromethane (900 mL). The combined organic layer is washed with water (450 mL), 5% sodium bicarbonate (450 mL), and water (450 mL). The solvent from the organic layer is evaporated at 45° C. Methanol (180 mL) is charged to the reaction mass and again the solvent is evaporated form the reaction mass completely at 45° C. under reduced pressure. Methanol (450 mL) is charged to the reaction mass and heated at reflux for 30 minutes. The solution is cooled to 25-35° C. and further cooled to −8 to −12° C. The reaction mass is maintained at −8 to −12° C. for 3 hours, the obtained solid is collected by filtration, washed with chilled methanol (90 mL), and dried at 50-60° C. to afford 44 g of the title compound.

1. customis allowed to 110° C.
2. temperaturemaintained for 2 hours
3. temperaturemaintained for 24 hours
4. temperatureFinally, the reaction mixture is maintained for 48 hours
5. extractionThe reaction mass is extracted with dichloromethane (900 mL)
6. customthe layers are separated
7. washthe aqueous layer is washed with dichloromethane (900 mL)
8. washThe combined organic layer is washed with water (450 mL), 5% sodium bicarbonate (450 mL), and water (450 mL)
9. customThe solvent from the organic layer is evaporated at 45° C
10. additionMethanol (180 mL) is charged to the reaction mass
11. customagain the solvent is evaporated form the reaction mass completely at 45° C. under reduced pressure
12. additionMethanol (450 mL) is charged to the reaction mass
13. temperatureheated
14. temperatureat reflux for 30 minutes
15. temperatureThe solution is cooled to 25-35° C.
16. temperaturefurther cooled to −8 to −12° C
17. temperatureThe reaction mass is maintained at −8 to −12° C. for 3 hours
18. filtrationthe obtained solid is collected by filtration
19. washwashed with chilled methanol (90 mL)
20. customdried at 50-60° C.