At large scale, ethyl acetoacetate is industrially produced by treatment of diketene with ethanol.

Thus ethyl acetoacetate behaves similarly to acetylacetone:[6] The resulting carbanion undergoes nucleophilic substitution.

Ethyl (and other) acetoacetates nitrosate readily with equimolar sodium nitrite in acetic acid, to afford the corresponding oximinoacetoacetate esters.

A dissolving-zinc reduction of these in acetic acid in the presence of ketoesters or beta-diketones constitute the Knorr pyrrole synthesis, useful for the preparation of porphyrins.

Another similarity to acetylacetone, ethyl acetoacetate forms chelate complexes, such as Al(CH3C(O)CHCO2C2H5)3[9] and the Fe(III) derivative.