Fast Amide Couplings in Water: Extraction, Column Chromatography, and Crystallization Not Required.

In the micelle of PS-750-M, the presence of 3° amides from the surfactant proline linker mimics dimethylformamide, dimethylacetamide, and N-methyl-2-pyrrolidone. The resultant micellar properties enable extremely fast amide couplings mediated by 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide (without hydroxybenzotriazole), rather than expensive and specialized coupling agents. Conditions have been developed wherein products precipitate, and isolation by filtration completely avoids the use of organic solvent. This methodology is scalable and avoids product epimerization.