Studies on the synthesis of β-keto esters derived from dipeptides: search for a low-epimerizing method

β-Keto esters derived from dipeptides are prepared by application of common methodologies employed for the synthesis of amino acid-derived β-keto esters; however, epimerization of the C-terminal residue occurred to different extents depending on the method. In imidazolide activated dipeptides, this epimerization is due to the CDI activation step and to the configurational instability of the intermediate imidazolides in different reaction media. Regarding yield and diastereomeric purity, the method of choice proved to be the reaction of dipeptide-derived imidazolide with the potassium salt of malonic half esters in the presence of MgCl2.