Copper-mediated reduction of 2-[¹⁸F]fluoroethyl azide to 2-[¹⁸F]fluoroethylamine

¹⁸F-labelled fluoroalkylamines are attractive reagents for the preparation of positron emission tomography tracers containing amine, amide, and N-heterocyclic moieties. Herein, we report that 2-[¹⁸F] fluoroethylamine can be obtained from 2-[¹⁸F]fluoroethyl azide by reduction with elemental copper under acidic conditions. Azide to amine reduction was achieved in near quantitative analytical yields within 30 min by heating a solution of 2-[¹⁸F]fluoroethyl azide in the presence of copper wire and aqueous trifluoroacetic acid. Subsequent reaction of 2-[ ¹⁸F]fluoroethylamine with benzoyl chloride in the presence of triethylamine provided N-[¹⁸F]fluoroethyl benzamide in 63% decay-corrected radiochemical yield from 2-[¹⁸F]fluoroethyl azide. The utility of the Cu(0)/H⁺ azide reduction method was further exemplified by preparation of the potential GABA_A tracer 9H-β-carboline N-2-[¹⁸F]fluoroethylamide, which was obtained in 46% decay-corrected radiochemical yield by reaction of 2-[¹⁸F] fluoroethylamine with the corresponding 9H-β-carboline pentafluorophenyl ester.