Abstract

Selective Thermal Deprotection of N-Boc Protected Amines in Continuous Flow

Anita Maguire, Professor of Pharmaceutical Chemistry, University College Cork

Among the various protecting groups employed to protect amines during synthetic steps, Boc protection has proved particularly effective. While removal of Boc protecting groups under acidic conditions is one of the most frequently encountered transformations within the chemical and pharmaceutical community, there are limitations including selectivity, compatibility with other acid labile groups, vigorous off-gassing and foaming. Thermal N-Boc deprotection of a range of amines is readily effected in continuous flow, in the absence of an acid catalyst. While the optimum results were obtained in methanol or trifluoroethanol, deprotection can be effected in a range of solvents of different polarities. Sequential selective deprotection of N-Boc groups has been demonstrated, as exemplified by effective removal of an aryl N-Boc group in the presence of an alkyl N-Boc group.