Novel synthesis of an [18F]aryl boronic acid ester as a reagent for 18F-labeling via Suzuki coupling

Abstract

Indirect 18F labeling methods using 18F-containing compounds such as N-succinimidyl-4-[18F]fluorobenzoate and 4-[18F]fluoroiodobenzene as labeling reagents have been reported because direct 18F labeling has difficulty in labeling aromatic compounds. In this study, we synthesized the 18F-labeling reagent 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) [18F]fluorobenzene ([18F]TDBFB) using a resonant-type microwave reactor in the presence of (2,2,6,6-tetramethylpiperidine 1-oxyl and a copper catalyst. Compared with a previous report on [18F]fluorophenylboronic acid, [18F]TDBFB was synthesized simply. Moreover, we applied [18F]TDBFB for the Suzuki coupling with triflate and bromide precursors. The Suzuki coupling of [18F]TDBFB and precursors using resonant-type microwave reactor yielded 4-[18F]fluorobiphenyl and the [18F]pitavastatin derivative as the coupling products. These results show the potential of [18F]TDBFB obtained using rapid synthesis as an indirect 18F-labeling reagent.