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 LiAlH 4 , reaction of alcohol with CBr 4 /PPh 3 , 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, a-carboxylation of tetralone with Me 2 CO 3 in the presence of NaH, reduction of ketone group with Et 3 SiH, 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 1 for the following free supplemental resource(s): Full experimental and spectral details.]

Synthesis of Pyridazine and Pyrrole Analogues of 2‐Aminotetralin as Potential Dopaminergics

“…The initially formed acyl azide was rearranged with the loss of nitrogen to afford the isocyanate, which was trapped in situ with benzyl alcohol. Refluxing the mixture in benzene afforded the benzyl carbamate 7 in 76% yield through the Curtius rearrangement . Inverse electron demand Diels–Alder additions (iEDDA) between 1,2,4,5‐tetrazines and olefins are very well known for the preparation of pyridazines .…”