S<sub>N</sub>Ar Radiofluorination with In Situ Generated [<sup>18</sup>F]Tetramethylammonium Fluoride
So Jeong Lee, María T. Morales-Colón, Allen F. Brooks, Jay S. Wright, Katarina J. Makaravage, Peter J. H. Scott, Melanie S. Sanford
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.
Topics & Concepts
NucleophileArylFluorideTetramethylammoniumReagentIn situChemistryCombinatorial chemistryOrganic chemistryInorganic chemistryCatalysisIonAlkylFluorine in Organic ChemistryInorganic Fluorides and Related Compounds