[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).