Pd0‐Mediated Cross‐Coupling of [11C]Methyl Iodide with Carboxysilane for Synthesis of [11C]Acetic Acid and its Active Esters: 11C‐Acetylation of Small, Medium, and Large Molecules

Abstract

AbstractA rapid Pd0‐mediated cross‐coupling of [11C]CH3I with carboxytriphenylsilane (1) to synthesize [2‐11C]acetic acid ([11C]2) and its corresponding imidyl esters as radiolabeling reagents for 11C‐acetylation is reported. The reaction of [11C]CH3I with 1 using a Pd2(dibenzylideneacetone)3/P(o‐tolyl)3 (1 : 4) catalyst in tetrahydrofuran/H2O (9 : 1) at 90 °C for 4 min afforded [11C]2 having satisfactory radioactivity and a good yield. The coupling of the cationic carbon atom of methyl iodide and the carboxyl group in 1 is an ionicity‐driven reversed‐polarity reaction. An injectable radiopharmaceutical formulation of [11C]2 prepared using 33 GBq of [11C]CH3I had a radioactivity of 7.4–7.8 GBq, and the decay‐corrected radiochemical yield of [11C]CH3I into [11C]2 was 63–73 %. [11C]2 was converted to [2‐11C]acetic acid phthalimidyl ester ([11C]3) or its succinimidyl ester ([11C]10), which were used for the 11C‐acetylation of 4‐aminophenol, oxytocin, and albumin. Injectable solutions of these products (0.25–2.0 GBq) are suitable for in vivo positron emission tomography studies.