Synthesis of N-Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids

Christopher A. Wilhelmsen, Alexandre D.C. Dixon, John D. Chisholm, Daniel A. Clark

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

N-Substituted 3-amino-4-halopyridines are valuable synthetic intermediates, as they readily provide access to imidazopyridines and similar heterocyclic systems. The direct synthesis of N-substituted 3-amino-4-halopyridines is problematic, as reductive aminations and base-promoted alkylations are difficult in these systems. A high yielding deprotection/alkylation protocol mediated by trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate is described, providing access to a wide scope of N-substituted 3-amino-4-halopyridines. This protocol furnishes many reaction products in high purity without chromatography. Similar reductive amination conditions were also established for deactivated anilines.

Original languageEnglish (US)
Pages (from-to)1634-1642
Number of pages9
JournalJournal of Organic Chemistry
Volume83
Issue number3
DOIs
StatePublished - Feb 2 2018

ASJC Scopus subject areas

  • Organic Chemistry

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