Methanol → (R)-5-Hydroxymethyltolterodine

Participants

Reaction Steps

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%.

Provenance & Evidence