A HIGHLY CONVERGENT SYNTHESIS OF BENZIMIDAZOLYLPIPERIDINES

The lithiation of suitably protected imidazoles and benzimidazoles has recently attracted considerable synthetic attention.1Of the various groups used to protect the imidazole nitrogen, the benzyl group is generally considered to be unsuitable due to problems of competing benzylic metalation.2 We have maintained a long-standing interest in the chemistry and pharmacology of 4-aroyl-piperidines. In this regard, we wished to prepare some 4-(2-benzimidazolyl)piperidines related to Astemizole (1), a recently marketed nonsedating antihistamine.3 We now report a convenient synthesis of benzimidazolylpiperidine 2, which relies on the acylation of l-(4-fluorobenzyl)-benzimidazole. The 4-fluorobenzyl group in this instance not only serves as a protecting group allowing C2-depro-tonation but also as a part of the desired pharmacophore. © 1990, American Chemical Society. All rights reserved.