Water → Rotigotine

A reaction vessel, equipped with a magnetic stirrer, a dropping funnel, and a pH meter was charged with 50 g of rotigotine hydrochloride at ambient temperature, and 750 mL of dichloromethane and 250 mL of water were added. The resulting mixture was stirred for about 20 minutes and the pH was adjusted to 6.5 by dropwise addition of about 170 mL of a 5% solution of sodium bicarbonate. The phases were separated, and the organic phase was washed twice with 250 mL each of water. The aqueous phase was washed with dichloromethane and the organic phases were combined and evaporated under vacuum to obtain a solid. Water (250 mL) was added to the solid and the volume was concentrated by distillation. Diethyl ether (10 mL) was added to the residue and evaporated to obtain a solid. n-hexane (500 mL) was added to the solid and the mixture was stirred overnight at room temperature. Crystals were formed and subsequently filtered, washed with 50 mL of n-hexane, and dried under vacuum to afford 42 g of crystalline rotigotine base Form I in 94% yield, having a purity of 99.9%, by HPLC.

1. customA reaction vessel, equipped with a magnetic stirrer, a dropping funnel
2. customThe phases were separated
3. washthe organic phase was washed twice with 250 mL each of water
4. washThe aqueous phase was washed with dichloromethane
5. customevaporated under vacuum
6. customto obtain a solid
7. concentrationthe volume was concentrated by distillation
8. additionDiethyl ether (10 mL) was added to the residue
9. customevaporated
10. customto obtain a solid
11. stirringthe mixture was stirred overnight at room temperature
12. customCrystals were formed
13. filtrationsubsequently filtered
14. washwashed with 50 mL of n-hexane
15. customdried under vacuum

ORD record

ord-a4a3882534aa4b0d8d0cabb505e887e2

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344165B2