Specific deuteromethylation by the eschweiler—clarke reaction. Synthesis of differently labelled variants of trimethylamine and their use for the preparation of labelled choline and acetylcholine

Reductive methylation (the Eschweiler-Clarke reaction) was used as a route for the synthesis of differently deuterium labelled variants of trimethylamine with the ultimate aim of preparing labelled variants of choline and acetylcholine. Combinations of unlabelled and labelled formaldehyde and formic acid yielded symmetrically labelled trimethylamines of high isotopic purity. The labelled congeners to acetylcholine and choline that were prepared subsequently provide suitable internal standards and tracers to be used in mass spectral analysis and in the evaluation of the pharmacokinetics of the parent compounds.