Synthesis of 2-substituted 4-pyridylpropionates. Part 1. Claisen condensation approach

Abstract

A synthesis of methyl 3-(2-methoxy-4-pyridyl)propionate (4), a key intermediate in the synthesis of the potent and long-acting histamine H₂-receptor antagonist SK&F 93574 (3), is described. The key steps in the synthesis of compound (4) are a Claisen ester condensation to give the intermediate (16) and a subsequent reduction step to give the ester (4). The reduction was found to be difficult and our investigations are described. In addition, alternative, but unsuccessful, approaches to the desired pyridylpropionate (4) are discussed.