Propylamine → 2-Propylamino-5-methoxytetralin

Participants

Reaction Steps

Another process for preparing racemic rotigotine hydrochloride, which is disclosed in U.S. Pat. No. 4,564,628, is shown in Scheme 2 below. 5-methoxy-2-tetralon (Compound I) is reacted with 3-propylamine in acetic acid and H2/PtO2 to obtain 1,2,3,4-tetrahydro-5-methoxy-N-propyl-2-naphthaleneamine (Compound VI). This intermediate then is reacted either with 2-thienylacetic acid in presence of borane trimethylamine complex in xylene or with 2-thienylacetyl chloride and lithium aluminum hydride to obtain 1,2,3,4-tetrahydro-5-methoxy-N-propyl-N-[2-(2-thienyl)ethyl]-2-naphthaleneamine (Compound IV). Finally, this intermediate is reacted with boron tribromide, then with HCl, to form the racemic rotigotine hydrochloride (Compound V).

Provenance & Evidence