Synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde

An efficient synthesis of [3-C-13]-2,3-dihydroxy-4-methoxybenzaldehyde, an isotopically labelled probe of a common intermediate used in the synthesis of a number of biologically relevant molecules, has been achieved in 9 steps from an acyclic, non-aromatic precursor. A C-13 label for molecular imaging was introduced in a linear synthesis from the reaction of [C-13] -labelled methyl iodide with glutaric monomethyl ester chloride. Cyclisation then aromatisation gave 1,3-dimethoxybenzene and an additional methoxy group was introduced by a formylation/Baeyer Villigerihydrolysisimethylation sequence. Subsequent ortho-formylation and selective demethylation yielded the desired [3-C-13]-2,3-dihydroxy-4-methoxybenzaldehyde. (C) 2015 Elsevier Ltd. All rights reserved.