18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

The F-18 syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [F-18]fluoride from H-2[O-18]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [F-18]fluoride is commonly achieved by phase transfer catalysts (PTC) in aqueous solution, which makes azeotropic drying indispensable. The ideal PTC is characterized by a slightly basic nature, its capacity to elute [F-18]fluoride with anhydrous solvents, and its efficient complex formation with [F-18]fluoride during subsequent labeling. Herein, we developed tri-(tert-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for F-18-fluorination reactions. The favorable elution efficiency of [F-18]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high F-18-recoveries of 96-99%. F-18-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing F-18-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to F-18-fluorination reactions and could be used for elution of [F-18]fluoride with MeOH, omitting an additional base and azeotropic drying prior to F-18-labeling. We speculate that the tert-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [F-18]fluoride during nucleophilic F-18-fluorination.

Automated summary

This study developed TBMA-I as a PTC for F-18-fluorination reactions, demonstrating its favorable elution efficiency and potential application in labeling reactions.