Synthesis of Methyl 7,9-Dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate and Its Analogues

Abstract

A high-yielding five-step synthesis of the title compound, methyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate, starting from 2,4-dimethylaniline was developed. This synthesis involved N-alkylation of 2,4-dimethyl­aniline with ethyl 4-bromobutyrate to obtain ethyl 4-[(2,4-dimethylphenyl)amino]butanoate. Carbamoylation of the latter followed by hydrolysis of the resulting ester provided 4-[(2,4-dimethylphenyl)(methoxycarbonyl)amino]butanoic acid. Activation of the carboxylic acid using thionyl chloride followed by intramolecular cyclization via a Friedel–Crafts reaction using aluminum trichloride provided the title compound in good yield. Analogues of the title compound were also prepared similarly.

Key words

alkylation - carbamoylation - hydrolysis - Friedel–Crafts reaction

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