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

Abstract 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(0), 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 5.2 GBq 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.