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Updated: Jun 24, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Facile reductive amination of aldehydes with electron-deficient anilines by acyloxyborohydrides in TFA: application
Eric E Boros1, James B Thompson, Subba R Katamreddy
1GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA. eric.e.boros@gsk.com
Abstract:
A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.
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