A combinatorially convenient version of synthesis of 5-substituted oxazole-4-carboxylic acid ethyl esters

Reaction of ethyl isocyanoacetic acid with sodium hydride in anhydrous benzene, followed by treatment with carboxylic acid chlorides or N-(acyloxy)pyrrolidine-2,5-diones, gives 5-substituted oxazole-4-carboxylic acid esters. The procedure is applicable to derivatives of various carboxylic acids, including saturated aliphatic, α,β-unsaturated, alicyclic, aromatic, heterocyclic, and N-Boc-protected amino acids.