Ishii, Hideki  ,  Minegishi, Katsuyuki  ,  Nagatsu, Koutarou  ,  Ming-Rong, Zhang

Objectives: Introduction of carbonyl group into an aryl or heteroaryl groups is useful method for the construction of valuable pharmacologically active compounds. However typical carbonylation methods using [11C]O generally requires high pressure and high temperature conditions. Therefore, the development of amenable method for the [11C]carbonylation reaction is needed. Here we present the Pd(0)-mediated mild [11C]carbonylation reaction using [11C]O and boronic acid esters under atmospheric pressure.1 ,2 Results and discussion: The carbonylation reaction was carried out using [11C]O in the presence of aryl and heteroaryl boronic acid esters, paradium(II) acetate (Pd(OAc2)), p-benzoquinone (PBQ) and triphenylphosphine (PPh3) in MeOH or DMF-MeOH (v/v =1:1). The reaction mixture was heated at 65 °C for 5 min under atmospheric pressure to give corresponding [carbonyl-11C]esters. Some of these [carbonyl-11C]esters were converted to corresponding [carbonyl-11C]amides by treating with 25% ammonia solution at 65 °C for 5 - 10 min. Using this methods, we have been succeeded the synthesis of various aryl/heteroaryl [carbonyl-11C]esters with decay-corrected radiochemical yield (RCY) in the range of 6-80%. The efficiency of the amidation was deeply affected by the structure of the substrate. Although [carbonyl-11C]salicylamide, nicotinamide, 3-quinolineamide, 4-isoquinolineamide and 4-hydroxybenzamide were obtained in good RCY from corresponding [carbonyl-11C]esters, the production of 4-benzyloxy[carbonyl-11C]benzamide was failed. Conclusions: Pd(0)-mediated [11C]carbonylation with aryl/heteroarylboronic acid pinacol esters and [11C]O have been carried out successfully in MeOH or DMF-MeOH (v/v =1:1) under atmospheric pressure at 65 °C for 5 min and gave the corresponding [carbonyl-11C]esters in the range of 6-80% RCY. Some of these [carbonyl-11C]esters were converted to the corresponding [carbonyl-11C]amides by treating with 25% ammonia solution.
Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry

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