Diisopropyl Ether → Fesoterodine fumarate

HRID 1473013Notes

Reaction equation

HRID 1473013 reaction equation
[CH3:1][CH:2]([C:4]([O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:29][OH:30])=[CH:11][C:12]=1[C@@H:13]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:14][CH2:15][N:16]([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])=[O:5])[CH3:3].ClC1C=CC=CC=1C(O)C([O-])=O.[OH-].[Na+].[C:45]([OH:52])(=[O:51])/[CH:46]=[CH:47]/[C:48]([OH:50])=[O:49].C(OC(C)C)(C)C>O>[CH3:3][CH:2]([C:4]([O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:29][OH:30])=[CH:11][C:12]=1[C@@H:13]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:14][CH2:15][N:16]([CH:20]([CH3:21])[CH3:22])[CH:17]([CH3:18])[CH3:19])=[O:5])[CH3:1].[CH:46](/[C:45]([OH:52])=[O:51])=[CH:47]\[C:48]([OH:50])=[O:49]

Participants

6

Reactant 4

HCID 7914Diisopropyl EtherHCID 14798Sodium HydroxideHCID 444972Fumaric AcidHCID 131732760HCID 131732760, compound

Product 1

HCID 9849808Fesoterodine fumarateYield 99.98%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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 IPA (240 ml) is added at 25° C. to 30° C. and then heated to 50° C. to 55° C. Fumaric acid (17 g) was added to the resulting mass was maintained for 30 minutes and further cooled to 25° C. to 30° C. followed by the addition of diisopropyl ether (840 ml) at 25° C. to 30° C. and maintained for 12 hours. The resulting mass was filtered, washed with diisopropyl ether (2×30 ml) and then dried under vacuum for 24 hours at 45° C. to 50° C. to afford Fesoterodine Fumarate (70 g) (Purity by HPLC: 99.98%).

Workup

  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 IPA (240 ml)
  15. additionis added at 25° C. to 30° C.
  16. temperatureheated to 50° C. to 55° C
  17. temperaturewas maintained for 30 minutes
  18. temperaturefurther cooled to 25° C. to 30° C.
  19. temperaturemaintained for 12 hours
  20. filtrationThe resulting mass was filtered
  21. washwashed with diisopropyl ether (2×30 ml)
  22. customdried under vacuum for 24 hours at 45° C. to 50° C.

Sources & evidence

ORD record
ord-bdfa77123c1e42d9a6b888e249b416bb
Source dataset
uspto-grants-2015_04
Patent number
US09012678B2

Reaction notes

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