A Non-anhydrous, Minimally Basic Protocol for the Simplification of Nucleophilic F-fluorination Chemistry

Overview

Journal Sci Rep

Specialty Science

Date 2020 Apr 24

PMID 32321927

Citations 12

Authors

J A H Inkster

V Akurathi

A W Sromek

Y Chen

J L Neumeyer

A B Packard

Affiliations

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Abstract

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [F]fluoride from an anion exchange cartridge with a basic solution of KCO or KHCO 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 [F]fluoride incorporation chemistry. In this approach, [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 F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [F]F from the anion-exchange cartridge. As proof-of-principle, "NAMB" chemistry was utilized for the synthesis of the dopamine D/D antagonist [F]fallypride.

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