Synthesis of ¹¹C‐Labelled Amides by Palladium‐Mediated Carboxamination Using [¹¹C]Carbon Monoxide, in situ Activated Amines and 1,2,2,6,6‐Pentamethylpiperidine

Twenty‐seven 11 C‐labelled amides were synthesised using [ 11 C]carbon monoxide in low concentrations, palladium(0), organohalides and amines in a small micro‐autoclave (200 μL). The focus of the study was to improve the radiochemical yields in this palladium‐mediated amide synthesis when employing less‐reactive amines, such as methylamine, [(2 R )‐1‐ethylpyrrolidin‐2‐yl]methylamine ( 40 ) and 2‐(pyridin‐2‐yl)ethanamine ( 41 ). The radiochemical yields were improved when utilizing 1,2,2,6,6‐pentamethylpiperidine (pempidine) in combination with the amine substrates. The 11 C‐labelled amides were obtained mostly in high radiochemical yields (in the range 16−94%) and the specific radioactivity varied between 650 and 1250 GBq/μmol. 1‐(1,3‐Benzodioxol‐5‐yl[ 13 C]carbonyl)piperidine (6a) was synthesised to verify the labelling position (δ = 169.8 ppm) using 13 C NMR spectroscopy. The radiochemical purity of the target compounds was determined by analytical HPLC and exceeded 95%. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)