Hydrochloric Acid → Pregabalin

Temperatur

22.5 °C

The tartarate salt of 3-aminomethyl N,N-diethyl-5-methyl hexanamide (10 grams) was dissolved in water (15 ml) and dichloromethane (25 ml) was added to it. The pH of reaction mixture was adjusted to 9-10 by addition of sodium hydroxide solution (3.0 grams in 3.0 ml of water) and stirred for 10-15 min at 20-25° C. The aqueous and organic layer was separated. The aqueous layer was extracted with dichloromethane. The solvent was distilled off from combined organic layer to obtain a residue. Potassium hydroxide (5.0 gram), water (10 ml) and methanol (10 ml) was added to the obtained residue and heated it to 70-75° C., the reaction was stirred at this temperature for 18 hours. The reaction mixture was cooled to 30° C. and the pH adjusted to 4.0 using concentrated hydrochloric acid. The reaction mixture was heated to 80° C. and stirred for 45 min and filtered. The filtrate was cooled to 5° C. The solid formed was filtered and washed with cool water. The solid was dried at 50-55° C. to yield (S)-Pregabalin.

1. customThe pH of reaction mixture
2. customThe aqueous and organic layer was separated
3. extractionThe aqueous layer was extracted with dichloromethane
4. distillationThe solvent was distilled off
5. customto obtain a residue
6. temperatureheated it to 70-75° C.
7. stirringthe reaction was stirred at this temperature for 18 hours
8. temperatureThe reaction mixture was cooled to 30° C.
9. temperatureThe reaction mixture was heated to 80° C.
10. stirringstirred for 45 min
11. filtrationfiltered
12. temperatureThe filtrate was cooled to 5° C
13. customThe solid formed
14. filtrationwas filtered
15. washwashed with cool water
16. customThe solid was dried at 50-55° C.

ORD-Eintrag

ord-d9c3b8c682124261aebbecad897ad0e1

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08168828B2