Cu‐Mediated Radiofluorination of Aryl Pinacolboronate Esters: Alcohols as Solvents with Application to 6‐L‐[18F]FDOPA Synthesis

Abstract

Cu‐mediated radiofluorination of arylboronic acid pinacol esters (ArylBPin) using Cu(OTf)2(Py)4 complex is a useful approach for the introduction of [18F]fluorine into non‐activated arenes and heteroarenes. Owing to the complexity of the mechanism and wide variation in substrate reactivity the choice of reaction conditions must be made individually for every precursor. Careful selection of phase‐transfer catalysts also plays a role, as Cu‐catalyst and ArylBPin precursors are known to be unstable in basic conditions. Using tetrabutylammonium triflate alcohol solution for elution of [18F]fluoride from ion‐exchange cartridge and employing same alcohol as a co‐solvent in the following labelling step, we have developed a general protocol resulting in >80 % fluorination efficiency of ArylBPin precursors for 4‐[18F]fluoro‐D,L‐phenylalanine and 6‐L‐[18F]FDOPA. Radiofluorination in neat alcohol was particularly effective for the synthesis of 6‐L‐[18F]FDOPA, allowing for substantial increase of yield and decrease of synthesis time compared to current methods (activity yield 14.5 ± 0.5 %, 70 min synthesis time).