Hofmann rearrangement of primary carboxamides and cyclic imides using DCDMH and application to the synthesis of gabapentin and its potential peptide prodrugs

Two protocols for the efficient transformation of aromatic as well as aliphatic primary carboxamides to the corresponding carbamates and aromatic as well as aliphatic cyclic imides to the corresponding anthranilic acid derivatives & amino acid derivatives, respectively, are described. We also developed a novel methodology to the multigram scale synthesis of gabapentin and (S)-pregabalin. The gabapentin methyl carbamate was converted to novel potential peptide prodrugs of gabapentin. (C) 2019 Elsevier Ltd. All rights reserved.