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A non-anhydrous, minimally basic protocol for the simplification of nucleophilic (18)F-fluorination chemistry

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [(18)F]fluoride from an anion exchange cartridge with a basic solution of K(2)CO(3) or KHCO(3) and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the...

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Detalles Bibliográficos
Autores principales: Inkster, J. A. H., Akurathi, V., Sromek, A. W., Chen, Y., Neumeyer, J. L., Packard, A. B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176689/
https://www.ncbi.nlm.nih.gov/pubmed/32321927
http://dx.doi.org/10.1038/s41598-020-61845-y
Descripción
Sumario:Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [(18)F]fluoride from an anion exchange cartridge with a basic solution of K(2)CO(3) or KHCO(3) and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the water. In this work we describe an alternative “non-anhydrous, minimally basic” (“NAMB”) technique that simplifies the process and avoids the basic conditions that can sometimes limit the scope and efficiency of [(18)F]fluoride incorporation chemistry. In this approach, [(18)F]F(−) is eluted from small (10–12 mg) anion-exchange cartridges with solutions of tetraethylammonium bicarbonate, perchlorate or tosylate in polar aprotic solvents containing 10–50% water. After dilution with additional aprotic solvent, these solutions are used directly in nucleophilic aromatic and aliphatic (18)F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [(18)F]F(-) from the anion-exchange cartridge. As proof-of-principle, “NAMB” chemistry was utilized for the synthesis of the dopamine D(2)/D(3) antagonist [(18)F]fallypride.