Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate

•Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.•Nucleophilic radiofluorination of the aromatic moiety with a radiochemical conversion of over 10%.•8.9±1.6% decay corrected radiochemical yield of radiochemically pure product.•The maximum specific activity value was 43 GBq/mmol.•A tertiary-butyl group was used as an effective leaving and directing group for radiofluorination.

An electrochemical method with the ability to conduct 18F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[18F]fluoro-l-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N·3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N·3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radio-fluorination efficiency of 10.4±0.6% (n=4) and specific activity of up to 43 GBq/mmol was obtained after 1 h electrolysis of 0.1 M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N·3HF (0.033 M) and NBu4PF6 (0.05 M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.