Automated Radiosynthesis of [

(S,S)-2-(α-(2-[18F]Fluoro[dideutero]methoxyphenoxy)benzyl)morpholine ([18F]FMeNER-D2), which is used to image the norepinephrine transporter in the brain via positron emission tomography (PET), is typically radiosynthesized by O-fluoromethylating norethylreboxetine (NER) with [18F]bromofluoromethane-d2 using a fully automated 18F-labeling synthesizer with a two-pot unit. We simplified the automated radiosynthesis of [18F]FMeNER-D2 through the use of a straightforward one-pot method to prepare [18F]fluoromethyl-d2-tosylate as the fluoromethylating agent (avoiding the need to azeotropically dry [18F]F- in advance), which was then reacted with NER. The reaction conditions were optimized, with [18F]FMeNER-D2 synthesized using an 18F-labeling synthesizer equipped with a one-pot unit. As a result, a synthesis time, radiochemical yield based on total [18F]F-, molar activity, and radiochemical purity of 66 ± 4.7 min (n = 7), 9.0% ± 0.8% (n = 3), 130-275 GBq/μmol (n = 7), and > 97% (n = 7), respectively, were obtained at the end of synthesis. In conclusion, we successfully synthesized [18F]FMeNER-D2 using a simplified one-pot, fully automated, 18F-fluoromethylation method in an 18F-labeling synthesizer.