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

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