Application of continuous flow technology to the expedient synthesis of isotopically substituted compounds

Isotopically modified compounds are of great importance to the scientific community owing to the large number of specific uses that exist for them; however, due to their low abundance associated costs are high. Once a small discrete isotopic precursor has been obtained, it must then be incorporated into a more complex molecule at the desired position which creates a major synthetic challenge owing to their limited availability. The difficulties encountered when obtaining isotopically enriched compounds result in phenomenal costs that mean even small quantities of simple molecules are extremely expensive to prepare; thus there is a need for expedient, cost effective and transferable syntheses involving isotopes.In contrast to traditional synthetic techniques, continuous flow systems provide a superior route to the preparation of such molecules viz allowing the use of small, highly contained systems, stoichiometric quantities of reagents and generic methodology to deliver products in high yields and purities. The work contained herein exemplifies that by applying small scale, continuous flow technology to the traditional problems of synthesis involving isotopes, either stable or unstable, new developments can be realised which allow the rapid, efficient, controlled and contained preparation of labelled molecules.General procedures have been developed which allow for the synthesis of isotopically substituted phenyl acetate, methoxybenzene, N-phenylacetamide and biphenyl derivatives in a timely manner using continuous flow systems. As proof of concept, small libraries comprising of compounds containing deuterium isotope labels were successfully prepared, generally in yields greater than 90% at a scale of 10’s mg