One-pot biocatalyzed preparation of substituted amides as intermediates ofpharmaceuticals

A lipase-catalyzed procedure is described for the one-pot conversion of car boxylic acids into substituted amides via in-situ formation of the ethyl es ter and subsequent aminolysis. The procedure was optimized for the preparat ion of tetrahydro-N-[3-(methylamino)-propyl]-2-furancarboxamide an intermed iate in the synthesis of Alfuzosin, a reducing agent of symptoms associated with benign prostatic hypertrophy. This methodology proved to be general a nd can be applied to open-chain, cyclic, hydroxy-, amino-, dicarboxylic, va rious chain lengths, and unsaturated acids. Moreover, the enzyme shows a re gioselective behavior in relation to primary and secondary amino groups. Th e procedure involved the treatment of the corresponding carboxylic acid wit h ethyl alcohol in presence of immobilized Candida antarctica lipase follow ed by addition of amine. The amide is obtained in good yields and regiosele ctive way. (C) 2001 Elsevier Science B.V. All rights reserved.