反应详情

温度

60 °C

Water (295 g) and rotigotine hydrochloride (120 g) followed by aqueous ammonia (25%, 111 g) and cyclohexane (295 g) are heated to reflux and agitated for 30-50 minutes. The mixture was cooled to 55-65° C. and the phases separated. Water (250 mL) is charged and the batch is heated to reflux for 30-50 minutes. The batch is cooled to 55-65° and the phases separated. The batch is then heated to reflux and cyclohexane/water is distilled until no further water is collected. The batch is then cooled to 70-78° C. If the volume of cyclohexane distilled off exceeds 15 mL then an equal amount to the cyclohexane that has been distilled off is charged to the batch. The organic phase is filtered through activated carbon and celite rinsing with cylohexane (110 g). The filterate was adjusted to 60-70° C. The batch is agitated at this temperature for 30-50 minutes. The batch is then cooled to 54-60° C. and rotigotine seed was added. After 15 minutes. The batch temperature is decreased to 37° C. in 5° C. intervals every 60 minutes. After 1 h stirring at 37° C. the batch is cooled to 25° C. and held 1 h at this temperature. The batch is then cooled and stirred at 6-12° C. for at least two hours. The slurry was then filtered and washed with cyclohexane (48 g). 101.5 g of rotigotine is obtained.

1. temperatureare heated
2. temperatureto reflux
3. customthe phases separated
4. additionWater (250 mL) is charged
5. temperaturethe batch is heated
6. temperatureto reflux for 30-50 minutes
7. temperatureThe batch is cooled to 55-65°
8. customthe phases separated
9. temperatureThe batch is then heated
10. temperatureto reflux
11. distillationcyclohexane/water is distilled until no further water
12. customis collected
13. temperatureThe batch is then cooled to 70-78° C
14. distillationIf the volume of cyclohexane distilled off
15. distillationan equal amount to the cyclohexane that has been distilled off
16. additionis charged to the batch
17. filtrationThe organic phase is filtered through activated carbon and celite
18. washrinsing with cylohexane (110 g)
19. customwas adjusted to 60-70° C
20. stirringThe batch is agitated at this temperature for 30-50 minutes
21. temperatureThe batch is then cooled to 54-60° C.
22. additionrotigotine seed was added
23. waitAfter 15 minutes
24. customis decreased to 37° C. in 5° C.
25. customevery 60 minutes
26. stirringAfter 1 h stirring at 37° C. the batch
27. temperatureis cooled to 25° C.
28. waitheld 1 h at this temperature
29. temperatureThe batch is then cooled
30. stirringstirred at 6-12° C. for at least two hours
31. filtrationThe slurry was then filtered
32. washwashed with cyclohexane (48 g)