Synthesis of piperidine analogs of 1‐(3‐chlorophenyl)piperazine, a well known serotonin ligand

Synthesis of arylpiperideines 3a‐3d and arylpiperidines 4a‐4d as analogs of a well known serotonin ligand 1‐(3‐chlorophenyl)piperazine is reported. Starting aryllithium derivatives were treated with 1‐methyl‐piperdin‐4‐one to provide the corresponding hydroxy derivatives 6a and 6b. N ‐Methylpiperideine derivatives 3a and 3c were obtained by their dehydration while the corresponding N ‐unsubstituted compounds 3b and 3d were prepared indirectly by a three‐step procedure. Hydrogenation of piperideine 3a provided the corresponding piperidine derivative 4a which after demethylation yielded 4b. Similar 4‐pyridyl derivatives 4c and 4d were prepared by a similar strategy via the corresponding methoxy derivatives.