Access to 18 F-labelled isoxazoles by ruthenium-promoted 1,3-dipolar cycloaddition of 4-[18 F]fluoro-N-hydroxybenzimidoyl chloride with alkynes.

4-[18 F]Fluoro-N-hydroxybenzimidoyl chloride (18 FBIC), an 18 F-labelled aromatic nitrile oxide, was developed as building block for Ru-promoted 1,3-dipolar cycloaddition with alkynes. 18 FBIC is obtained in a one-pot synthesis in up to 84% radiochemical yield (RCY) starting from [18 F]fluoride with 4-[18 F]fluorobenzaldehyde (18 FBA) and 4-[18 F]fluorobenzaldehyde oxime (18 FBAO) as intermediates, by reaction of 18 FBAO with N-chlorosuccinimide (NCS). 18 FBIC was found to be a suitable and stable synthon to give access to 18 F-labelled 3,4-diarylsubstituted isoxazoles by [Cp*RuCl(cod)]-catalysed 1,3-dipolar cycloaddition with various alkynes. So the radiosynthesis of a fluorine-18-labelled COX-2 inhibitor [18 F]1b, a close derivative of valdecoxib, was performed with 18 FBIC and 1-ethynyl-4-(methylsulfonyl)benzene, providing [18 F]1b in up to 40% RCY after purification in 85 minutes. The application of 18 FBIC as a building block in the synthesis of 18 F-labelled heterocycles will generally extend the portfolio of available PET radiotracers.