Methanol → (R)-5-Hydroxymethyltolterodine

HRID 1473009Notes

Reaction equation

HRID 1473009 reaction equation
C([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][OH:16])=[CH:11][C:10]=1[C@@H:17]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:18][CH2:19][N:20]([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])C1C=CC=CC=1.CO.C1(C)C=CC=CC=1>[Pd].O>[CH:24]([N:20]([CH:21]([CH3:23])[CH3:22])[CH2:19][CH2:18][C@@H:17]([C:10]1[CH:11]=[C:12]([CH2:15][OH:16])[CH:13]=[CH:14][C:9]=1[OH:8])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([CH3:26])[CH3:25]

Participants

6

Reactant 3

HCID 887MethanolHCID 1140TolueneHCID 15434420HCID 15434420, compound

Product 1

HCID 9819382(R)-5-Hydroxymethyltolterodine

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

11 L (R)-[4-Benzyloxy-3-(3-diisopropylamino-1-phenylpropyl)-phenyl]-methanol solution formula (H) and Pd/C (10%, 0.18 Kg) and methanol (30 L) was added in SS autoclave cell at 25° C. to 35° C. and the mixture was hydrogenated with 4 kg pressure at 25° C. to 35° C. for 2 hours. The mixture was then filtered and to the filtrate add 4.1 g sodium borohydride portion wise within 15-30 minutes at 25° C. to 35° C. and stir the reaction mass for 30 minutes. Methanol is distilled out under vacuum below 55° C. Further, reaction mass is cooled to 25° C. to 35° C. Toluene (10.0 L) was added followed by addition of RO water (1.50 L). The reaction mass is heated to 50° C. to 55° C. and maintained for 30 minutes. The layers were separated and to the organic layer add toluene (1.6 L) 25° C. to 35° C. The reaction mass is heated to 65° C. to 70° C. and maintain for 30 minutes. Further cooled to 25° C. to 35° C. and stirred for 2 hours and further cooled to 0° C. to 5° C. and stirred for 30 minutes. The reaction mass is washed with toluene (2×0.25 L) to afford the title compound as (R)-2-(3-diisopropylamino-1-phenylpropyl)-4-hydroxy methyl phenol having impurity X content about 0.03%.

Workup

  1. filtrationThe mixture was then filtered and to the filtrate
  2. additionadd 4.1 g sodium borohydride portion wise within 15-30 minutes at 25° C. to 35° C.
  3. distillationMethanol is distilled out under vacuum below 55° C
  4. customFurther, reaction mass
  5. temperatureis cooled to 25° C. to 35° C
  6. temperatureThe reaction mass is heated to 50° C. to 55° C.
  7. temperaturemaintained for 30 minutes
  8. customThe layers were separated and to the organic layer
  9. additionadd toluene (1.6 L) 25° C. to 35° C
  10. temperatureThe reaction mass is heated to 65° C. to 70° C.
  11. temperaturemaintain for 30 minutes
  12. temperatureFurther cooled to 25° C. to 35° C.
  13. stirringstirred for 2 hours
  14. temperaturefurther cooled to 0° C. to 5° C.
  15. stirringstirred for 30 minutes
  16. washThe reaction mass is washed with toluene (2×0.25 L)

Sources & evidence

ORD record
ord-5848622065324480a47a9dbf7e107612
Source dataset
uspto-grants-2015_04
Patent number
US09012678B2

Reaction notes

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