反应详情

温度

65 °C

A reactor was charged sequentially with 6,7-dimethoxy-quinoline-4-ol (1 L, 10.0 kg) and acetonitrile (64.0 L). The resulting mixture was heated to approximately 65° C. and phosphorus oxychloride (POCl3, 50.0 kg) was added. After the addition of POCl3, the temperature of the reaction mixture was raised to approximately 80° C. The reaction was deemed complete (approximately 9.0 hours) when <2% of the starting material remained (in process high-performance liquid chromatography [HPLC] analysis). The reaction mixture was cooled to approximately 10° C. and then quenched into a chilled solution of dichloromethane (DCM, 238.0 kg), 30% NH4OH (135.0 kg), and ice (440.0 kg). The resulting mixture was warmed to approximately 14° C., and phases were separated. The organic phase was washed with water (40.0 kg) and concentrated by vacuum distillation with the removal of solvent (approximately 190.0 kg). Methyl-t-butyl ether (MTBE, 50.0 kg) was added to the batch, and the mixture was cooled to approximately 10° C., during which time the product crystallized out. The solids were recovered by centrifugation, washed with n-heptane (20.0 kg), and dried at approximately 40° C. to afford the title compound (8.0 kg).

1. temperaturethe temperature of the reaction mixture was raised to approximately 80° C
2. temperatureThe reaction mixture was cooled to approximately 10° C.
3. customquenched into a chilled solution of dichloromethane (DCM, 238.0 kg), 30% NH4OH (135.0 kg), and ice (440.0 kg)
4. temperatureThe resulting mixture was warmed to approximately 14° C.
5. customphases were separated
6. washThe organic phase was washed with water (40.0 kg)
7. concentrationconcentrated by vacuum distillation with the removal of solvent (approximately 190.0 kg)
8. additionMethyl-t-butyl ether (MTBE, 50.0 kg) was added to the batch
9. temperaturethe mixture was cooled to approximately 10° C., during which time the product
10. customcrystallized out
11. customThe solids were recovered by centrifugation
12. washwashed with n-heptane (20.0 kg)
13. customdried at approximately 40° C.