AN ALTERNATIVE SYNTHESIS OF THE NMDA ANTAGONIST CGS-19755 VIA FREE-RADICAL CARBAMOYLATION OF ETHYL ISONICOTINATE

The NMDA antagonist CGS 19755 (cis-4-phosphonomethyl-2-piperidinecarbo xylic acid) has been prepared by applying Minisci reaction conditions [formamide, hydrogen peroxide, iron(II) sulfate] to ethyl isonicotinat e, reduction of the ester with sodium borohydride, alcoholysis of the 2-carboxamide, formation of 4-(diethylphosphonomethyl)-2-pyridinecarbo xyl hydrogenation of the pyridine nucleus, and acid hydrolysis. The ov erall, unoptimized yield was around 11%. The procedure employs cheap s tarting materials, is practical and avoids the use of toxic and hazard ous cyanotrimethylsilane which is used in the published procedure.