Sodium Hydroxide → Fesoterodine fumarate

Temperature

80 °C

Fesoterodine 2-Chloro-mandelate (85 g), water (425 ml) and MDC (225 ml) were added to a four-neck two liter round bottom flask at 25° C. to 35° C. The reaction mass is cooled to 0° C. to 5° C. The pH was adjusted to 10 to 10.5 by addition of 10% sodium hydroxide solution at 0° C. to 5° C. Temperature of the reaction mass is raised to 25° C. to 35° C. and maintained for 30 minutes. The layers were settled and separated. Further, to the MDC layer water (255 ml) is added at 25° C. to 35° C. and further cooled to 0° C. to 5° C. and pH was adjusted to 10 to 10.5 by addition of 10% sodium hydroxide solution. The temperature of the reaction mass is raised to 25° C. to 35° C. and maintained for 30 minutes. The layers were settled and separated. To the MDC layer activated charcoal (4.2 g) is added and stirred for 30 minutes. The resulting mass was filtered and washed with MDC (2×42.5 ml) and to the obtained resulting mass methyl ethyl ketone (170 ml) is added at 25° C. to 30° C. and stirred for 10 minutes and then heated to 80° C. Fumaric acid (21.5 g) was added to the resulting mass, stirred for 1 hour at 80° C. followed by the drop wise addition of cyclohexanc (70 ml) at 80° C. and stirred for 1 hour. The resulting mass was slowly cooled to 25° C. to 30° C. and stirred for 12 hours at the same temperature. The resulting mass was then cooled to 0° C. to 5° C. and stirred for 12 hours at 0° C. to 5° C. The separated solid was filtered, washed with the mixture of cyclohexane (135 ml) and methyl ethyl ketone (15 ml), and then dried under vacuum at 45° C. to 50° C. to afford Fesoterodine Fumarate (70 g) (Purity by HPLC: 99.95%).

1. temperatureThe reaction mass is cooled to 0° C. to 5° C
2. temperatureTemperature of the reaction mass is raised to 25° C. to 35° C.
3. temperaturemaintained for 30 minutes
4. customseparated
5. additionFurther, to the MDC layer water (255 ml) is added at 25° C. to 35° C.
6. temperaturefurther cooled to 0° C. to 5° C.
7. additionpH was adjusted to 10 to 10.5 by addition of 10% sodium hydroxide solution
8. temperatureThe temperature of the reaction mass is raised to 25° C. to 35° C.
9. temperaturemaintained for 30 minutes
10. customseparated
11. additionTo the MDC layer activated charcoal (4.2 g) is added
12. filtrationThe resulting mass was filtered
13. washwashed with MDC (2×42.5 ml) and to the obtained
14. customresulting mass methyl ethyl ketone (170 ml)
15. additionis added at 25° C. to 30° C.
16. stirringstirred for 10 minutes
17. stirringstirred for 1 hour at 80° C.
18. additionfollowed by the drop wise addition of cyclohexanc (70 ml) at 80° C.
19. stirringstirred for 1 hour
20. temperatureThe resulting mass was slowly cooled to 25° C. to 30° C.
21. stirringstirred for 12 hours at the same temperature
22. temperatureThe resulting mass was then cooled to 0° C. to 5° C.
23. stirringstirred for 12 hours at 0° C. to 5° C
24. filtrationThe separated solid was filtered
25. washwashed with the mixture of cyclohexane (135 ml) and methyl ethyl ketone (15 ml)
26. customdried under vacuum at 45° C. to 50° C.

ORD record

ord-ccea308543a04b41a1c8a11d956a64a1

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012678B2