Potassium Carbonate → (R)-5-Hydroxymethyltolterodine

Temperature

55 °C

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).

1. custombrought to 50° C.
2. waitAt the end, the two phases are left
3. customto separate
4. washthe organic phase is washed with 2000 ml of deionised water, still at the temperature of 50° C
5. concentrationThe organic phase is then concentrated to residue
6. customobtaining a white solid which
7. customis recovered with 400 ml of toluene
8. customto obtain a complete solution
9. customA white solid precipitates
10. temperatureby cooling to 25° C
11. temperatureThe suspension is maintained at 25° C. for two hours
12. temperatureit is further cooled to 2° C.
13. temperaturemaintained in such conditions for one hour
14. filtrationThe obtained solid is filtered
15. washwashed with three 100 ml portions of toluene
16. customdried under vacuum for 8 hours at 45° C.

ORD record

ord-a04628e9c1064d49ad26a5c4a344722f

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946456B2