Synthesis of F-18-Difluoromethylarenes from Aryl (Pseudo) Halides

摘要

A general method for the synthesis of [F-18]difluoromethylarenes from [F-18]fluoride for radiopharmaceutical discovery is reported. The method is practical, operationally simple, tolerates a wide scope of functional groups, and enables the labeling of a variety of arenes and heteroarenes with radiochemical yields (RCYs, not decay-corrected) from 10 to 60%. The F-18-fluorination precursors are readily prepared from aryl chlorides, bromides, iodides, and triflates. Seven F-18-difluoromethylarene drug analogues and radiopharmaceuticals including Claritin, fluoxetine (Prozac), and [F-18]DAA1106 were synthesized to show the potential of the method for applications in PET radiopharmaceutical design.