Abstract
A method has been developed for the carbon‐14 radiosynthesis of [^14^C]XEN‐D0401, a 4‐(2‐hydroxyphenyl)quinolin‐2(1__H__)‐one derivative. The radiosynthetic route involves a series of ortho‐lithiations directed by both 2‐methoxymethyl (MOM) and pivaloyl protecting groups. This is demonstrated in the first key radiochemical step between the reaction of 5‐chloro‐2‐methoxymethoxy‐[carboxyl‐^14^C]benzoic acid methyl ester [^14^C]‐3 and the __ortho‐__lithiated intermediate generated from 2,2‐dimethyl‐N‐(4‐trifluoromethylphenyl)‐propionamide (2) to afford the protected benzophenone [^14^C]‐4. The other key radiochemical step utilizes a variation of the Friedländer quinoline synthesis, which involves a base catalysed, one‐pot condensation process between (2‐amino‐5‐trifluoromethyl‐phenyl)‐(5‐chloro‐2‐methoxymethoxy‐phenyl)‐[^14^C]methanone [^14^C]‐5 and γ‐butyrolactone to give MOM‐protected [^14^C]‐6. On MOM deprotection, [^14^C]XEN‐D0401 was isolated with a radiochemical purity of >97%, with a specific activity of 55 mCi/mmol from seven radiochemical steps, starting from barium [^14^C]carbonate in a radiochemical yield of 10.5%. Copyright © 2010 John Wiley & Sons, Ltd.