Radiochemical Synthesis of Alkyl Geminal 18F-Difluoroalkyl Motifs Mediated by Silver(I) Oxide

Abstract

18F radiotracers are used in positron emission tomography imaging for medical diagnosis and drug development. Current methods to synthesize 18F-polyfluorinated functional groups are limited in substrate scope and result in radiotracers with low molar activities (Am). We disclose the synthesis of a range of 18F-difluoroalkyl groups by nucleophilic substitution of geminal bromofluoroalkyl electrophiles with [18F]fluoride mediated by Ag2O. The utility of this transformation to support (pre)clinical imaging is demonstrated by translation to an automated synthesizer.