Novel synthesis of benzofuran- and indol-2-yl-methanamine derivatives

We report on a novel synthesis towards benzofuran-2-yl-methanamine and indol-2-yl-methanamine derivatives by using ortho-methoxy and ortho-nitro substituted phenylacetic acids as starting material, respectively. For each compound series, a key intermediate bearing the oxazole-4-carboxylic acid methylester moiety was produced. Refluxing the ortho-methoxy series in HBr/HAc produced the desired benzofuran-2-yl-methanamines. Accordingly, for the synthesis of indoles the nitro-group was first reduced and refluxing these intermediates in HCl gave the corresponding indol-2-yl-methanamines. The method worked well with electron donating substituents. Limitations regarding electron withdrawing substituents are discussed. This straightforward synthetic procedure can be a useful approach to generate a variety of substituted benzofuran-2-yl-methanamine and indol-2-yl-methanamine compounds by starting from readily available phenylacetic acid derivatives.