Selective Amidation of Unprotected Amino Alcohols Using Surfactant-in-Water Technology: A Highly Desirable Alternative to Reprotoxic Polar Aprotic Solvents

A general selective and environmentally friendly method for the formation of amide bonds using a surfactant in water as medium is described. The use of readily available 1-ethy1-3-(3-(dimethylamino)propyl)-carbodiimide (EDC) and hydroxybenzotriazol (HOBt) as a coupling system, N-methylmorpholine (NMM), and TPGS-750-M represents mild conditions allowing for chemoselective amidation of unprotected amino alcohols. Comparative results with classical polar aprotic solvents such as dimethylformamide or acetonitrile are presented.