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Updated: Oct 30, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of α-substituted indolylacetamide using acetonitriles as acetamide enolate equivalents through O-transfer
Takumi Abe1, Kenta Noda1, Daisuke Sawada1
1Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 7008530, Japan. t-abe@okayama-u.ac.jp dsawada@okayama-u.ac.jp.
Abstract:
We introduce readily available ammonium hemiaminals as O-transfer reagents and commercially available acetonitriles as a primary amide enolate precursor. The combination serves as an amide enolate equivalent, thereby providing one-pot access to α-substituted indolylacetamides. A broad substrate scope and good functional group tolerance as well as gram-scale synthesis make this protocol highly attractive. Mechanistic experiments suggest that the cyano group is trapped by a hydroxy group of hemiaminals en route to the desired primary amides under metal-free conditions.
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