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Updated: Mar 3, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
2,2,2-Trifluoroethanol as a solvent to control nucleophilic peptide arylation
Diana Gimenez1, Anica Dose, Nicholas L Robson
1Durham University, Department of Chemistry, South Road, Durham, DH1 3LE, UK. s.l.cobb@durham.ac.uk.
Abstract:
The SNAr arylation of peptides with perfluoroaromatics provides a route by which to install a useful chemical handle that enables both 19F-NMR analysis and further chemical modification. However, chemo-selective arylation in peptides containing multiple nucleophilic side chains currently presents a challenge to the field. Herein, we demonstrate that employing 2,2,2-trifluoroethanol (TFE) as a solvent in peptide SNAr reactions significantly improves nucleophile-selectivity when compared to N,N'-dimethylformamide (DMF).
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