A comparative study on Suzuki‐type ¹¹C‐methylation of aromatic organoboranes performed in two reaction media

Abstract

The Suzuki-type cross coupling reaction is a palladium-mediated multistep reaction that has been used to synthesize several 11 C-labeled tracers for PET.However, the impact of the selected organoborane reagent and reaction medium on the radiochemical yield (RCY) has not been thoroughly investigated. To bridge this gap, we studied the synthesis of 1-[ 11 C]methylnaphthalene using four different organoborane precursors in reactions performed in DMF/water and THF/water. In the synthesis of 1-[ 11 C]methylnaphthalene, the best radiochemical yields (RCYs), approximately 50%, were obtained with boronic acid and pinacol ester precursors, whereas less than 4% RCY was obtained when performing the reaction with the N-methylimidodiacetic acid boronic ester (MIDA ester) precursor. 1-[ 11 C] methylnaphthalene was obtained in higher yields in almost all syntheses performed in THF/water as compared to DMF/water. This observation was in line with previously reported results for [ 11 C]UCB-J, a tracer for the synaptic vesicle glycoprotein 2A (SV2A) receptor, that also was obtained in higher RCY when synthesized in THF/water. The same trend was observed with [ 11 C] cetrozole, where the RCY was more than doubled in THF/water compared to the previously published synthesis performed in DMF. These results suggest that THF/water could be the preferred reaction medium when producing PET tracers via the Suzuki-type coupling reaction.

Recent Developments in Carbon-11 Chemistry and Applications for First-In-Human PET Studies

“…For an overview of 11 C-C cross-coupling strategies, we refer the reader to a comprehensive review from H. Doi [ 59 ]. Recent progress in the field has been made by Rokka et al, who systematically studied the reaction of various organoborane precursors with [ 11 C]methyl iodide in two different reaction media, DMF(/water) and THF/water, to determine the best precursor and solvent for Suzuki-type cross coupling reactions in 11 C-chemistry [ 60 ]. These authors found that for their model compound (1-[ 11 C]methylnaphthalene), the boronic acid and pinacol ester precursors gave the highest yields, while the solvent mixture THF/water was equal or superior in any tested reaction.…”