Novel synthesis of 11 C-labeled imidazolines via Pd(0)-mediated 11 C-carbomethoxylation using [ 11 C]CO and arylborons

A labeling technique was developed for the imidazoline I receptor ligand 2-(3-fluoro-tolyl)-4, 5-dihydro-1H-imidazole (FTIMD) using Pd(0)-mediated C-carbomethoxylation with [ C]CO, followed by imidazoline ring formation with ethylenediamine-trimethylaluminium (EDA-AlMe ). To achieve this, [ C]CO was passed through a methanol (MeOH) solution containing 3-fluoro-4-methylphenylboronic acid (1), palladium (II) acetate (Pd [OAc] ), triphenylphosphine (PPh ), and p-benzoquinone (PBQ). The mixture was then heated at 65°C for 5 min. EDA was introduced into the reaction mixture, and MeOH was completely evaporated at temperatures exceeding 100°C. The dried reaction mixture was combined with an EDA-AlMe (1:1) toluene solution and heated at 145°C for 10 min. Portions of the reaction mixture were analyzed through high-performance liquid chromatography, resulting in [ C]FTIMD with 26% (n = 2) decay-corrected radiochemical yield (RCY). This method could be utilized for various arylborons to produce [2- C]imidazolines 4a-h with RCYs ranging from low to moderate. Notably, [2- C]benazoline was obtained with a moderate RCY of 65%. The proposed technique serves as an alternative to the Grignard method, which uses [ C]CO to generate a [2- C]-labeled imidazoline ring.