11C]/(13C)Carbon monoxide in palladium-mediated synthesis of imides

Abstract

[11C]Carbon monoxide in low concentration with palladium(0) complexes (in the range of 5 µmol) and aryl halides (about 10 µmol) were used in the synthesis of the 11C-labelled imides, thalidomide, N-phthaloyl-L-glutamic acid, N-phthaloylhexane and aniracetam. The labellings were performed with ring closure reactions except in the case of aniracetam. These imides were obtained in nearly quantitative radiochemical yields, calculated from the [11C]carbon monoxide, with specific radioactivities between 70–600 GBq µmol−1. The radiochemical purity of the LC-purified products exceeded 98%. N-(13C)Phthaloyl-L-glutamic acid 2 was produced to verify the position of the label (δ 167.5 ppm) with 13C NMR, and this also indicates that the discussed approach is valuable for labelling with other carbon isotopes. In a typical experiment starting with 2.8 GBq of [11C]carbon monoxide, 0.6 GBq of HPLC-purified [11C]-N-phthaloyl-L-glutamic acid 2 was obtained within 40 minutes from the start of the carbonylation reaction (84% decay-corrected radiochemical yield).