Hydrochloric Acid → [2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopentyl-acetic acid

Participants

Reaction Steps

To a ice-cold suspension of 8.10 g (15.91 mmol) N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide in 45 ml tetrahydrofuran and ml water were added dropwise over 30 min. a solution of 6.68 g (159 mmol) lithium hydroxide monohydrate in 32.50 ml (318 mmol) 30% hydrogen peroxide solution and 15 ml water. After stirring for 4.5 h at room temperature, 150 ml water and 100 ml ethyl acetate were added and the pH adjusted to 1 using 25% aqueous hydrochloric acid. The phases were separated and the aqueous phase extracted three times with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution and brine, then dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate:methanole (100:0:0 to 0:100:0 to 0:85:15). Off-white solid (55%). MS (Turbo Spray): m/z=391.1 [M+H].

Provenance & Evidence