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

Abstract

AbstractTwenty‐seven 11C‐labelled amides were synthesised using [11C]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, [(2R)‐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 11C‐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[13C]carbonyl)piperidine (6a) was synthesised to verify the labelling position (δ = 169.8 ppm) using 13C 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)