A Practical Method for Functionalized Peptide or Amide Bond Formation in Aqueous−Ethanol Media with EDC as Activator

Abstract

Selective formation of amides or peptides with ethanol as solvent using a convenient one-pot procedure in which acid activating agent N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) is simply added to a mixture of the carboxylic acid, amine, catalytic HOBt (1-hydroxy benzotriazole), and NMM (N-methylmorpholine) as base has been developed. Sensitive functionalities such as hydroxyl groups are well tolerated under the reaction conditions. In addition, isolation of products is usually by simple filtration from the reaction media. The scope and generality of this methodology was investigated.