An alternative synthesis of the NMDA antagonist CGS 19755 via free radical carbamoylation of ethyl isonicotinate.

I Martin, J Anvelt, L Vares, I Kühn, A Claesson

Index: Acta Chem. Scand. 49(3) , 230-2, (1995)

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Abstract

The NMDA antagonist CGS 19755 (cis-4-phosphonomethyl-2-piperidinecarboxylic acid) has been prepared by applying Minisci reaction conditions [formamide, hydrogen peroxide, iron(II) sulfate] to ethyl isonicotinate, reduction of the ester with sodium borohydride, alcoholysis of the 2-carboxamide, formation of 4-(diethylphosphonomethyl)-2-pyridinecarboxylate, hydrogenation of the pyridine nucleus, and acid hydrolysis. The overall, unoptimized yield was around 11%. The procedure employs cheap starting materials, is practical and avoids the use of toxic and hazardous cyanotrimethylsilane which is used in the published procedure.