General and Scalable Amide Bond Formation with Epimerization-Prone Substrates Using T3P and Pyridine
Joshua R. Dunetz, Yanqiao Xiang, Aaron Baldwin and Justin Ringling
*Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, United States, Email: joshua.r.dunetzpfizer.com
J. R. Dunetz, Y. Xiang, A. Baldwin, J. Ringling, Org. Lett., 2011, 13, 5048-5051.
DOI: 10.1021/ol201875q (free Supporting Information)
The mild combination of T3P (n-propanephosphonic acid anhydride) and pyridine enables a low-epimerization amide bond formation. This robust and practical method is general for the coupling of various racemization-prone acid substrates and amines, including relatively non-nucleophilic anilines, and provides amides in high yields with very low epimerization.
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