Dehydrative Condensation of Carboxylic Acids with Amines Promoted by HBF4/MS 5A

Abstract The direct dehydrative condensation of carboxylic acids with amines is one of the most straightforward methods for the synthesis of amides. We discovered that HBF 4 effectively promotes the coupling of several N ‐protected amino acids in the presence of molecular sieves (MS) 5A to afford the corresponding peptides in good to high yield. Interestingly, the recovered MS 5A could be reused as a catalyst even in the absence of additional HBF 4 for the dehydrative condensation. This protocol is not limited to the synthesis of peptides, but generally works for the synthesis of amides from a variety of carboxylic acids and amines.