Development, Optimization, and Scope of the Radiosynthesis of 3/5- F-18 Fluoropyridines from Readily Prepared Aryl(pyridinyl) iodonium Salts: The Importance of TEMPO and K₂CO₃

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. (authors)