Development, Optimization, and Scope of the Radiosynthesis of 3/5-[ 18 F]Fluoropyridines from Readily Prepared Aryl(pyridinyl) Iodonium Salts: The Importance of TEMPO and K 2 CO 3

Abstract : A robust process for the radiosynthesis of 3/5-[18F]fluoropyridines has been developed by radiofluorination of iodonium triflates using K18F/K2CO3/K222 complex in the presence of TEMPO. Both electronically deficient and enriched iodonium salts were readily obtained from the corresponding 3/5-iodopyridines and afforded the corresponding 3/5-[18F]fluoropyridines in 6–78% yields. The concentrations of K2CO3 and TEMPO were found to be crucial for the radiofluorination efficiency. The process was validated using two automated systems for the 18F-radiolabeling of 2-chloro and 2-carboxamido-5-fluoropyridines carried out in 10–20% yields.