Rapid synthesis of [¹⁸F]SR46349B, a potent and selective 5‐HT₂ receptor antagonist

F‐18 labeled SR46349B, a highly potent and selective 5‐HT₂ receptor antagonist, was synthesized as a potential radioligand for PET studies of brain 5‐HT₂ receptors. Nucleophilic aromatic substitution of trans‐1‐(2‐nitrophenyl)‐3‐(4‐methoxymethoxyphenyl)‐2‐propenone (10) with NCA [¹⁸F]fluoride in the presence of potassium carbonate and kryptofix‐222, followed by HCl hydrolysis, gave F‐18 labeled 12, which was purified by a novel combination of C‐18 Sep‐Pak and silica column chromatography. Subsequent condensation of [¹⁸F]ketone 12 with Me₂NCH₂CH₂ONH₂ gave a mixture of [¹⁸F]SR46349B and its geometric isomer, which was separated by high performance liquid chromatography. The three step hot synthesis of [¹⁸F]SR46349B required 170 min. and gave a specific activity of 1140 Ci/mmol, 5% radiochemical yield (EOB) and 96% radiochemical purity.