反应详情

Aluminium chloride (3.747 kg) was added to dichloromethane (7.0 l) at room temperature and propionyl chloride (1.297 kg) was then added over a 10 minute period. The mixture was stirred for 45 minutes and then a solution of 4-bromoanisole (1.312 kg) in dichloromethane (0.87 l) was added over a 15 minute period. The mixture was heated under reflux for 6.5 hours and then kept overnight at room temperature. The ice-cooled reaction mixture was quenched by the slow addition of ice (15 kg) over 1.5 hours. The mixture obtained was stirred for 15 minutes, the layers were separated and the aqueous layer extracted with dichloromethane (2×1.0 l). The organic layers were combined and washed with water (2×2.0 l), then two-thirds of the solvent removed by distillation at atmospheric pressure. Methanol (5.63 l) was then added slowly and the distillation continued until a pot temperature of 64° C. and a head temperature of 62° C. was achieved. Water (0.4 l) was added slowly and the mixture was cooled resulting in the precipitation of an off-white solid. Further water (0.4 l) was then added slowly and the precipitated solid granulated at about 10° C. for 2 hours. The solid was then filtered off, washed sparingly with a 6:1 methanol/water mixture and dried under reduced pressure at 50° C. to provide the title compound (1.464 kg).

1. temperatureThe mixture was heated
2. temperatureunder reflux for 6.5 hours
3. waitkept overnight at room temperature
4. customreaction mixture
5. customwas quenched by the slow addition of ice (15 kg) over 1.5 hours
6. customThe mixture obtained
7. stirringwas stirred for 15 minutes
8. customthe layers were separated
9. extractionthe aqueous layer extracted with dichloromethane (2×1.0 l)
10. washwashed with water (2×2.0 l)
11. customtwo-thirds of the solvent removed by distillation at atmospheric pressure
12. additionMethanol (5.63 l) was then added slowly
13. distillationthe distillation
14. customcontinued until a pot temperature of 64° C.
15. customa head temperature of 62° C.
16. additionWater (0.4 l) was added slowly
17. temperaturethe mixture was cooled
18. customresulting in the precipitation of an off-white solid
19. waitthe precipitated solid granulated at about 10° C. for 2 hours
20. filtrationThe solid was then filtered off
21. washwashed sparingly with a 6:1 methanol/water mixture
22. customdried under reduced pressure at 50° C.