SYNTHESIS OF 4,4-DISUBSTITUTED PIPERIDINE ANALOGS OF (+ LETHYL)-3-METHYL-4-PIPERIDYL]-N-PHENYLPROPANAMIDE/

Condensation of (+/-)-1-benzyl-3-methyl-4-piperidone (1) with aniline followed by trapping of the intermediate imine with cyanide generated a mixture of isomeric nitriles 2A and 2B, the structures of which were established unambiguously by obtaining an X-ray crystal structure on nitrile 2B. Subsequent elaboration of the nitrile intermediates provid ed analogs of ylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide havin g a second substituent (carbomethoxyl, carboethoxyl, methoxymethyl) at the piperidine 4-position. The conversion of the carboxamide intermed iates 3A and 3B to the carboalkoxyl intermediates 5A, 5B and 6A was ac complished utilizing a modified esterification procedure. Proton nmr d ata are presented for both the final products and the key synthetic in termediates.