PROCESS FOR THE PREPARATION OF (6S)-(-)-5,6,7,8-TETRAHYDRO-6-[PROPYL-(2-THIENYL)ETHYL]AMINO-1-NAPHTHOL (ROTIGOTINE)

摘要

The present invention describes a novel process for the preparation of (6S)-(-)-5,6,7,8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) comprising: (a) acetylating (S)-(-)-5-hydroxy-N-n-propyl-2-aminotetraline to afford the acetate; (b) reacting this acetate, (-)-5-acetoxy- N-n-propyl-2-aminotetraline, with 2-(2-thienyl)ethanol 2- nitrobenzenesulfonate; (d) hydrolyzing (6S)-(-)-1-acetoxy-5, 6,7,8- tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthalene to afford (6S)-(- )-5, 6, 7, 8-tetrahydro-6-[propyl-(2-thienyl)ethyl]amino-1-naphthol (Rotigotine) and (d) purifying rotigotine either by the acetylation reaction and subsequent hydrolysis of the formed acetate or by salification of rotigotine through hydrochloride or hydrobromide formation and subsequent base release. Rotigotine is a dopamine agonist and is indicated for the treatment of Parkinson's disease.