S_NAr Radiofluorination with In Situ Generated [¹⁸F]Tetramethylammonium Fluoride

Abstract

This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [18F]KF·K2.2.2 and Me4NHCO3 for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [18F]Me4NF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [18F](hetero)aryl fluoride products in good to excellent radiochemical yields in the presence of ambient air/moisture. The reaction is applied to the preparation of 18F-labeled HQ-415 for potential (pre)clinical use.