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Updated: Jun 9, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
18F-Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [18F]Fluoride
Sebastiano Ortalli1, Joseph Ford1, Robert Szpera1
1Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Abstract:
Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative 18F-fluorodecarboxylation with [18F]fluoride affording biologically relevant 18F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [18F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including N-heteroarylation and amide as well as sulfonamide bond formation.
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