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

Abstract

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