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

• Main Authors: Sandip S. Shinde (Author), Kim-Viktoria Bolik (Author), Simone Maschauer (Author), Olaf Prante (Author)
• Format: Book
• Published: MDPI AG, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

The ¹⁸F syntheses of tracers for positron emission tomography (PET) typically require several steps, including extraction of [¹⁸F]fluoride from H₂[¹⁸O]O, elution, and drying, prior to nucleophilic substitution reaction, being a laborious and time-consuming process. The elution of [¹⁸F]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 [¹⁸F]fluoride with anhydrous solvents, and its efficient complex formation with [¹⁸F]fluoride during subsequent labeling. Herein, we developed tri-(<i>tert</i>-butanol)-methylammonium iodide (TBMA-I), a quaternary ammonium salt serving as the PTC for ¹⁸F-fluorination reactions. The favorable elution efficiency of [¹⁸F]fluoride using TBMA-I was demonstrated with aprotic and protic solvents, maintaining high ¹⁸F-recoveries of 96-99%. ¹⁸F-labeling reactions using TBMA-I as PTC were studied with aliphatic 1,3-ditosylpropane and aryl pinacol boronate esters as precursors, providing ¹⁸F-labeled products in moderate-to-high radiochemical yields. TBMA-I revealed adequate properties for application to ¹⁸F-fluorination reactions and could be used for elution of [¹⁸F]fluoride with MeOH, omitting an additional base and azeotropic drying prior to ¹⁸F-labeling. We speculate that the <i>tert</i>-alcohol functionality of TBMA-I promotes intermolecular hydrogen bonding, which enhances the elution efficiency and stability of [¹⁸F]fluoride during nucleophilic ¹⁸F-fluorination.

Item Description

10.3390/ph14090833
1424-8247