Synthesis of 3-[(2S)-azetidin-2-ylmethoxy]-5-[11C]-methylpyridine, an analogue of A-85380, via a Stille coupling

Article abstract of DOI:10.1002/jlcr.569

3-[(2S)-azetidin-2-ylmethoxy]-5-[¹¹C]-methylpyridine (5d), which might be a novel ligand for nicotinic receptors, was synthesized via coupling [¹¹C]iodomethane with tert-butyl (2S)-2-({[5-(trimethylstannyl)pyridin-3-yl]oxy}methyl) azetidine-1-carboxylate (4) at 80°C for 5 min with tri-o-tolylphosphine-bound, unsaturated palladium(O), followed by deprotection using trifluoroacetic acid (TFA). The previous problem (solid-phase extraction before injection on semi-preparative LC) with automation of Stille coupling reactions has been overcome. In a typical experiment, 0.46 GBq of 5d was obtained from 5.2GBq of [¹¹C]iodomethane. The decay-corrected radiochemical yield was 39% (based on the quantity [¹¹C]iodomethane trapped). The synthesis time was 43 min from end of radionuclide production. During a production condition using 36 μAh of proton beam irradiation, a specific radioactivity of 50 GBq/ μmol of the final product was obtained in biological buffer. Copyright