Synthesis of (R) and (S) 3-aminoquinuclidine-[3-14C] enantiomers, important components of a variety of 5-HT3 ligands

3-Aminoquinuclidine, an important fragment associated with many 5-HT (serotonin) receptor ligands, has been synthesized using a 14 C-carbonation based sequence to prepare the starting material, isonicotinic 14 C-acid (6). Elaboration of (6) to α-bromoacetyl-[ 14 C] isonipecotic acid (10) via the corresponding diazoketone, followed by intramolecular cyclization, gave the key intermediate 3-quinuclidone-[3- 14 C] (3). 3-quinuclidone-[3- 14 C] was converted to a mixture of phenethylamine diastereomers. Carrier free crystallization and hydrogenolysis furnished both (R) and (S) 3-aminoquinuclidine-[3- 14 C] enantiomers at >99% optical purity.