Methanol → (S)-Hydroxy Iloperidone

Temperature

0 °C

56.36 g of boran complex of (3aR,7R)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2c][1,3,2]oxazaborole (1 equivalent) is dissolved under nitrogen in methylenchloride, and the solution is cooled to 0° C. A 1M solution of 1-(4-{3-[4-(6-fluoro-benzo[d]isoxazol-3-yl)piperidin-1-yl]propoxy}-3-methoxy-phenyl)-ethanone (Iloperidone; 1 equivalent) in methylenchloride is added via a dropping funnel over 90 minutes while the internal temperature is maintained at 0° C.±2° C. After the addition is complete, the mixture is stirred at 0° C. for 20 hours. The reaction mixture is then poured into precooled methanol (0-5° C.) during 1 hour. The solution is warmed to room temperature and stirred until the H2 evolution ceases. The solution is concentrated by distillation and the residue dried in vacuum, treated with methanol and stirred for about 1 hour at 50° C. and an additional hour at 0° C. The product is isolated by filtration and dried under reduced pressure for 3 hours at 50° C. The title compound is obtained (white crystals).

1. temperatureis maintained at 0° C.±2° C
2. additionAfter the addition
3. temperatureThe solution is warmed to room temperature
4. stirringstirred until the H2 evolution ceases
5. concentrationThe solution is concentrated by distillation
6. customthe residue dried in vacuum
7. additiontreated with methanol
8. stirringstirred for about 1 hour at 50° C. and an additional hour at 0° C
9. customThe product is isolated by filtration
10. customdried under reduced pressure for 3 hours at 50° C

ORD record

ord-204dc5099bef432b895b7269f1dc8c9f

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08314129B2