Lactams. XII. Improvements in the Synthesis of Ethyl trans-5-Ethyl-2-oxo-4-piperidineacetate

A highly stereoselective, efficient synthetic route to ethyl trans-5-ethyl-2-oxo-4-piperidineacetate (11a) from 1-benzyl-2,4-dioxo-5-ethylpiperidine (2) is described. The steps involved are conversion of 2 into 1-benzyl-5-ethyl-2-oxo-1,2,5,6-tetrahydropyridine (6) through the lactam alcohol (5), the Michael condensation of 6 with diethyl malonate followed by alkaline hydrolysis, decarboxylation of the resulting trans-lactam dicarboxylic acid (8a) to the trans-lactam acid (9a), and debenzylation of 9a followed by esterification