title: General and scalable amide bond formation with epimerization-prone substrates using T3P and pyridine.
abstract: The mild combination of T3P (n-propanephosphonic acid anhydride) and pyridine has been developed for low-epimerization amide bond formation and implemented for the synthesis of a key intermediate to a glucokinase activator. This robust 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. With easy reaction setup and product isolation, this protocol offers several practical and experimental benefits.
authors.affiliation: Chemical Research and Development, Pfizer Worldwide Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. joshua.r.dunetz@pfizer.com
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Dunetz
authors.forename: Yanqiao
authors.initials: Y
authors.lastname: Xiang
authors.forename: Aaron
authors.initials: A
authors.lastname: Baldwin
authors.forename: Justin
authors.initials: J
authors.lastname: Ringling
mesh_terms: D000577:Amides / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D063065:Organophosphonates / Q000737:chemistry*; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000577:Amides; D063065:Organophosphonates; D011725:Pyridines; C569209:n-propanephosphonic acid anhydride; C023666:pyridine; D011407:Propane