No abstract

A new procedure has been developed for the synthesis of I4C-labeled glutethimide with an improved yield from K14CN. In this procedure benzyl cyanide prepared from benzyl chloride and K14CN was almost quantitatively monoethylated by an ion-pair extraction method using 50% excess of tetrabutylammonium hydroxide as the catalyst. Michael addition of methyl acrylate to monoethylbenzyl cyanide followed by hydrolysis with H2SO4 gave glutethimide which was then nitrated (HNO3 + H2SO4) and catalytically reduced to aminoglutethimide. The best result was obtained when the intermediate =-nitroglutethimide was isolated in pure form by crystallization and then reduced in the presence of 10% Pd/C. When the nitration product (which was a mixture of isomers) was reduced without purification, isolation of pure p-aminoglutethimide was more difficult and the yield was much lower.