An efficient synthesis of fenoprofen has been successfully achieved, featuring a Corey-Chaykovsky epoxidation reaction and a BF₃-catalyzed semi-pinacol rearrangement reaction. This newly developed protocol is amenable to the syntheses of ibuprofen, hexaprofen and biprofen. This research provides a solid basis for further development of novel processes for the production of these pharmaceutically important molecules. The semi-pinacol rearrangement reaction was a stepwise process. The isotope-labeling experiments indicated that this rearrangement took place intramolecularly rather than intermolecularly, in agreement with the [1,2] hydride shift mechanism.

Key words: fenoprofen, NSAID, semi-pinacol rearrangement, efficient synthesis