Synthesis of [ 11 C]/[ 13 C]Acrylamides by Palladium‐Mediated Carbonylation

Two methods are presented for the synthesis of acrylamides labelled with 11 C (β + , t 1/2 = 20.4 min) and 13 C in the carbonyl position. In the first method, [1‐ 11 C]acrylic acid is synthesised from [ 11 C]carbon monoxide by palladium‐mediated hydroxycarbonylation of acetylene. The labelled carboxylic acid is converted into the acyl chloride and subsequently treated with amine to yield N ‐benzyl[ carbonyl ‐ 11 C]acrylamide. The second method utilizes [ 11 C]carbon monoxide in a palladium‐mediated carbonylative cross‐coupling of vinyl halides and amines. A higher radiochemical yield is achieved with the latter method and the amount of amine needed is decreased to 1/20. The 11 C‐labelled acrylamides were isolated in up to 81 % decay‐corrected radiochemical yield. Starting from 10 ± 0.5 GBq of [ 11 C]carbon monoxide, N ‐benzyl[ carbonyl ‐ 11 C]acrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq μmol –1 . Co‐labelling with 11 C and 13 C enabled confirmation of the labelled position by 13 C NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)