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.