SYNTHESIS OF (R)-3-AMINOQUINUCLIDINE-[3-C-14] AND (S)-3-AMINOQUINUCLIDINE-[3-C-14] 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 C-14- carbon ation based sequence to prepare the starting material, isonicotinic C- 14-acid (6). Elaboration of (6) to alpha-bromoacetyl-[C-14] isonipecot ic acid (10) via the corresponding diazoketone, followed by intamolecu lar cyclization, gave the key intermediate 3-quinuclidone-[3-C-14] (3) . 3-quinuclidone-[3-C-14] was converted to a mixture of phenethylamine diastereomers. Carrier free crystallization and hydrogenolysis furnis hed both (R) and (S) 3-aminoquinuclidine-[3-C-14] enantiomers at >99% optical purity.