Fast and efficient copper-mediated ¹⁸F-fluorination of arylstannanes, aryl boronic acids, and aryl boronic esters without azeotropic drying

Background

Copper-mediated radiofluorination is a straightforward method to produce a variety of [¹⁸F]fluoroarenes and [¹⁸F]fluoroheteroarenes. To minimize the number of steps in the production of ¹⁸F-labelled radiopharmaceuticals, we have developed a short and efficient azeotropic drying-free ¹⁸F-labelling method using copper-mediated fluorination. Our goal was to improve the copper-mediated method to achieve wide substrate scope with good radiochemical yields with short synthesis time.

Results

Solid phase extraction with Cu (OTf)₂ in dimethylacetamide is a suitable activation method for [¹⁸F]fluoride. Elution efficiency with Cu (OTf)₂ is up to 79% and radiochemical yield (RCY) of a variety of model molecules in the crude reaction mixture has reached over 90%. Clinically relevant molecules, norepinephrine transporter tracer [¹⁸F]NS12137 and monoamine transporter tracer [¹⁸F]CFT were produced with 16.5% RCY in 98 min and 5.3% RCY in 64 min, respectively.

Conclusions

Cu (OTf)₂ is a suitable elution agent for releasing [¹⁸F]fluoride from an anion exchange cartridge. The method is fast and efficient and the Cu-complex is customizable after the release of [¹⁸F]fluoride. Alterations in the [¹⁸F]fluoride elution techniques did not have a negative effect on the subsequent labelling reactions. We anticipate this improved [¹⁸F]fluoride elution technique to supplant the traditional azeotropic drying of [¹⁸F]fluoride in the long run and to concurrently enable the variations of the copper-complex.