Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides

This report describes the development of a Zn(OTf)(2)-mediated method for converting alpha-tertiary haloamides to the corresponding fluorine-18 labelled alpha-tertiary fluoroamides with no-carrier-added [F-18]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.

Automated summary

This report presents the development of a Zn(OTf)(2)-mediated method for converting alpha-tertiary haloamides to the corresponding alpha-tertiary fluoroamides. Under optimized conditions, high radiochemical conversion can be achieved. This method has been successfully applied to prepare various model radiofluorides.