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

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.

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