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-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.
Martin
I
I
Department of Bioorganic Chemistry, Institute of Chemistry, Tallinn, Estonia.
Anvelt
J
J
Vares
L
L
Kühn
I
I
Claesson
A
A
D005609:Free Radicals / Q000737:chemistry; D007539:Isonicotinic Acids / Q000737:chemistry*; D015394:Molecular Structure; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D010875:Pipecolic Acids / Q000138:chemical synthesis*
D005609:Free Radicals; D007539:Isonicotinic Acids; D010875:Pipecolic Acids; C094021:ethyl isonicotinate; C053672:selfotel; D016202:N-Methylaspartate