First Synthesis of Dopamine and Rotigotin Analogue 2-Amino-6,8-dimethoxy-1,2,3,4-tetrahydronaphthalene

Abstract The title compound was synthesized starting from 3-(3,5-dimethoxyphenyl)acrylic acid in 11 steps with 30% total yield. The reaction sequence hydrogenation of acrylic acid, reduction of acid to alcohol derivative with LiAlH4, reaction of alcohol with CBr4/PPh3, substitution reaction of alkyl halide to nitrile derivative with NaCN, hydrolysis of nitrile with NaOH, cyclization reaction of acid with PPA to give 1-tetralone, α-carboxylation of tetralone with Me2CO3 in the presence of NaH, reduction of ketone group with Et3SiH, hydrolysis of ester, Curtius rearrangement of acid with diphenylphosphoryl azide followed by conversion to carbamate, and finally hydrogenolysis of carbamate afforded 2-amino-6,8-dimethoxy-1,2,3,4-tetrahydronaphthalene hydrogen chloride salt. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]