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Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
A Ni-Mediated Cross-Coupling Approach to Deuterated 18F- Fluoromethylated (Hetero)arenes
Maddison Lovell1, Sebastiano Ortalli1, Raquel Sánchez-Bento2
1Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
None:
Herein, we report a Ni-mediated 18F,D2-monofluoromethylation of (hetero)arenes from (pseudo)halide coupling partners. This new approach offers key advantages compared to traditional radiochemistry based on SN2-type reactivity with [18F]fluoride. These include increased precursor stability and availability, obviating bespoke precursor syntheses, broad functional group tolerance, and the late-stage introduction of deuterium and fluorine-18 in a single step, all features facilitating early access to PET ligands for discovery campaigns. This novel protocol is applied to over 30 diverse substrates, including complex bioactive molecules, and is amenable to scale-up via a semiautomated protocol on a commercial platform, illustrated by isolation of a 18F,D2-labeled PARP radiotracer.
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