One-pot esterification and amidation of phenolic acids

We developed a new one-pot reaction of phenolic acids to afford the corresponding esters and amides through acyl-protected and activated phenolic acid intermediates. The simultaneous protection/activation of phenolic acids with alkylchloroformates proceeded readily in the presence of DMAP at room temperature; subsequent addition of alcohols or amines afforded the corresponding esters or amides. The use of iso-butyloxycarbonyl as the protecting and activating group in the one-pot reactions afforded phenolic esters or amides in 91% average yield. As a practical example of this convenient synthesis, caffeic acid phenethyl ester (CAPE) was readily synthesized from commercially available caffeic acid and phenethyl alcohol in 95% yield, and an isotopomer of CAPE, [3,10-C-13(2)]CAPE, was synthesized in 91% yield from [3-C-13]caffeic acid and 2-[1-C-13]phenethyl alcohol. This method may be useful for the convenient esterification and amidation of diverse phenolic acids. (C) 2014 Elsevier Ltd. All rights reserved.