Expedient synthesis of deuterium‐labelled amides within micro‐reactors

Abstract

AbstractThe pharmaceutical industry relies heavily on the synthesis of small quantities (10–500 mg) of stable, isotopically labelled compounds in the evaluation of new drug candidates for metabolism studies. As a result of the phenomenal cost of labelled materials even the preparation of small quantities can be extremely expensive.In this paper, for the first time, we report that micro‐reactor technology may be used to prepare stable deuterium‐labelled compounds by conducting all optimization experiments using unlabelled precursors and simply substituting the labelled derivatives once the optimization is complete. Here, we wish to present a simple, general procedure for the synthesis of amides containing isotopic labels demonstrated using [C‐2H3]acetyl chloride 1. The reaction is carried out within a micro‐reactor set‐up which we believe offers superiority over other reported methods viz requiring stoichiometric quantities of reagents, high containment of the system and generality of the technique, obtaining products in high yields. Copyright © 2007 John Wiley & Sons, Ltd.