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

In the micelle of PS-750-M, the presence of 3 degrees amides from the surfactant proline linker mimics dimethylforma-mide, 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.