The synthesis of 3-(4-aminotetrafluorophenyl)-3-ethylpiperidine-2,6-dione; a fluorinated derivative of aminoglutethimide

Abstract

In investigating the role of the amino function of aminoglutethimide [3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione, (1)] in the inhibition of the cholesterol side-chain cleavage enzyme system desmolase and the estrogen-forming system aromatase, 4-amino-2,3,5,6-tetrafluoroglutethimide (4) has been synthesised. Attempts to proceed via 2,3,5,6-tetrafluoro-4-nitroglutethimide (5) failed due to the marked susceptibility of the fluorine substituents ortho to the nitro group to nucleophilic displacement. Compound (4) was prepared via pentafluoro-glutethimide (6), and exhibited moderate inhibition of desmolase but was a very weak inhibitor of aromatase.