Synthesis of C-14 labeled Rac-(3R,2S)-glycopyrronium bromide

In an effort to better understand the drug metabolism and pharmacokinetics (DMPK) properties of glycopyrronium bromide (1), a muscarinic acetylcholine receptor antagonist, a C-14 labeled isotopologue was required. The compound was prepared in five synthetic steps and 5% overall radiochemical yield from Cu¹⁴ CN. During the synthesis, an unexpected decarboxylation of phenylglyoxylate resulted in the loss of much of the radiolabeled compound. Chiral chromatography was utilized to isolate and deliver the proper pair of enantiomers as [¹⁴ C]-1.