Beating the hydrogen bond:: First selective and high-yielding N-acylation process for an α,β-diaminoalcohol

The first selective and high-yielding N-acylation of an alpha,beta-diaminoalcohol is reported, as well as the first use as N-acylation agent of a S-mercaptobenzothiazolyl thioester of an alpha,beta-unsaturated carboxylic acid. Other conventional coupling methods (acid chloride, uronium salt, carbonyl diimidazole, phosphonium salt) gave low yields respectively difficult to purify mixtures of N- and O,N-diacylated product (4b), due to the unusually high reactivity of the primary hydroxyl group caused by an intramolecular hydrogen bond to the dialkylamino moiety in the beta-position. Both the cinnamic thioester preparation and the coupling step were safely and reproducibly scaled up to a chromatography-free process in the pilot plant.