Potassium Carbonate → (R)-5-Hydroxymethyltolterodine

Participants

Reaction Conditions

Reaction Steps

260 g of (R)-2-[3-(Diisopropylamino)-1-phenylpropyl]-4-(hydroxymethyl)phenol (R)-2-acetoxy(phenyl)acetate and 2600 ml of toluene are introduced into a 10-liter reactor. 2600 ml of a 10% potassium carbonate solution are added to the mixture, brought to 50° C., and it is stirred for two hours. At the end, the two phases are left to separate and the organic phase is washed with 2000 ml of deionised water, still at the temperature of 50° C. The organic phase is then concentrated to residue, obtaining a white solid which is recovered with 400 ml of toluene and heated to 55° C. to obtain a complete solution. A white solid precipitates by cooling to 25° C. The suspension is maintained at 25° C. for two hours, then it is further cooled to 2° C. and maintained in such conditions for one hour. The obtained solid is filtered, washed with three 100 ml portions of toluene and dried under vacuum for 8 hours at 45° C., obtaining 116 g of the desired compound (70% yield).

Provenance & Evidence