Development of an Efficient Synthesis for a Nipecotate-Containing Immunopotentiator

The preparation of Elanco Animal Health immunopotentiator ( S )-ethyl-1-(2-thiopheneacetyl)-3-piperidinecarboxylate ( 1 ) is described. The synthesis includes a new resolution of racemic ethyl nipecotate with dibenzoyl- l -tartaric acid. The resolved salt is found to couple directly with commercially available 2-thiopheneacetyl chloride under environmentally friendly Schotten−Baumann conditions to afford the amide in high yield. The final product is an oil which is purified by wiped film evaporative distillation.