Synthesis of 2-substituted 4-pyridylpropionates. Part 2. Alkylation approach

A synthesis of methyl 3-(2-methoxy-4-pyridyl)propionate (2), a key intermediate in the synthesis of the potent long-acting histamine H2-receptor antagonist SK&F 93574 (1), is described. The key step in the synthesis of compound (1) involves alkylation of 2-methoxy-4-methylpyridine (5) with sodium chloroacetate in the presence of sodamide. The scope and limitations of the alkytation is investigated using a variety of electrophiles. The application of this reaction to other 2-substituted 4-methylpyridines is also discussed.