Synthesis of 14 C‐labeled piperidines and application to synthesis of [ 14 C]SCH 351125, a CCR5 receptor antagonist

1‐Benzyl‐4‐hydroxy[2‐ 14 C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [ 14 C]formaldehyde in high yield. The distribution pattern of 14 C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [ 14 C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐ 14 C]piperidine in six steps. [ 14 C]SCH 351125 is a mixture of four atropisomers. Preparation of [ 14 C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.