p-Toluenesulfonic acid → 5-methoxy-N-(2-(thiophen-2-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-amine

Beteiligte Stoffe

Reaktionsschritte

The preparation of racemic rotigotine hydrochloride is disclosed in U.S. Pat. No. 4,564,628. The process, which is depicted in Scheme 1, comprises reacting 5-methoxy-2-tetralone (Compound I) with β-(2-thienyl)ethylamine in presence of p-toluenesulfonic acid and sodium cyanoborohydride to obtain 1,2,3,4-tetrahydro-5-methoxy-N-[2-(thienyl)-ethyl]-2-naphthaleneamine (Compound II), which is reacted with propionyl chloride in presence of triethylamine to obtain N-(1,2,3,4-tetrahydro-5-methoxy-2-naphthenyl)-N-[2-(2-thienyl)ethyl)]propaneamide (Compound III). This propanamide is reduced with lithium aluminum hydride to obtain 1,2,3,4-tetrahydro-5-methoxy-N-propyl-N-[2-(2-thienyl)ethyl]-2-naphthaleneamine (Compound IV), which is subsequently reacted with boron tribromide, then hydrochloric acid (HCl) to form the racemic rotigotine hydrochloride (Compound V).

Herkunft & Nachweise