Abstract The synthesis of (E)-N-[methyl-d 3]-4-(3-pyridinyl)-3-buten-1-amine ([methyl-d 3] RJR 2403;[methyl-d 3] metanicotine) is reported. The incorporation of deuterium was performed during the first step of the synthesis via N-methylation of the pyrrolidine nitrogen of racemic nornicotine with [methyl-d 3] iodomethane, in the presence of n-BuLi at− 70 C to afford racemic [methyl-d 3] nicotine in high yield (91%). The pyrrolidine ring was then ...
