An azeotropic drying‐free approach for copper‐mediated radiofluorination without addition of base

Copper‐mediated radiofluorination provides a quick and versatile approach for ¹⁸F‐labeling of arenes and heteroarenes. However, this method is known to be base sensitive, which has been a barrier for preparative scale radiosynthesis. In this report, we provide an approach for copper‐mediated radiofluorination without azeotropic drying or adding a base. ¹⁸F]Fluoride trapped on a PS‐HCO₃ Sep‐Pak was quantitatively eluted with a solution of 4‐dimethylaminopyridinium trifluoromethanesulfonate (DMAP·OTf) in anhydrous N,N‐dimethylformamide (DMF). The eluted solution was directly used for copper‐mediated radiofluorination. Twelve boronic ester substrates were tested, yielding fluorinated products in 27% to 83% radiochemical yield based on HPLC analysis. This approach was successfully applied to the radiosynthesis of ¹⁸F]flumazenil, a well‐known positron emission tomography (PET) tracer for imaging central benzodiazepine receptors, with a radiochemical yield of 47%. This highly efficient protocol significantly augments the powerful copper‐mediated radiofluorination approach.