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

A labeling technique was developed for the imidazoline I₂ receptor ligand 2-(3-fluoro-tolyl)-4, 5-dihydro-1H-imidazole (FTIMD) using Pd(0)-mediated ¹¹C-carbomethoxylation with [¹¹C]CO, followed by imidazoline ring formation with ethylenediamine-trimethylaluminium (EDA-AlMe₃). To achieve this, [¹¹C]CO was passed through a methanol (MeOH) solution containing 3-fluoro-4-methylphenylboronic acid (1), palladium (II) acetate (Pd [OAc]₂), triphenylphosphine (PPh₃), 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 [¹¹C]FTIMD with 26% (n = 2) decay-corrected radiochemical yield (RCY). This method could be utilized for various arylborons to produce [2-¹¹C]imidazolines 4a–h with RCYs ranging from low to moderate. Notably, [2-¹¹C]benazoline was obtained with a moderate RCY of 65%. The proposed technique serves as an alternative to the Grignard method, which uses [¹¹C]CO to generate a [2-¹¹C]-labeled imidazoline ring.