Hydrochloric Acid → 2-(4-Chloro-phenyl)-1-[1-cyclohexyl-2-(pyridin-3-yloxy)-ethyl]-5,6-difluoro-1H-benzoimidazole

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Reaction Steps

To a solution of 46 mg (0.48 mmol) 3-hydroxypyridine in 3 mL N,N-dimethylformamide were added 21 mg (0.48 mmol, 55% dispersion in mineral oil) sodium hydride. The reaction mixture was stirred for 10 min. at room temperature. To this suspension 0.2 g (0.44 mmol) 1-(2-bromo-1-cyclohexyl-ethyl)-2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole (Ex. 34, int.) were added and the reaction mixture stirred for 4 days at room temperature. The reaction mixture was poured on 30 mL 1N hydrochloric acid and 30 mL ethyl acetate and the phases separated. The aqueous layer was extracted with 30 mL ethyl acetate. The combined organic layers were washed twice with 30 mL water and once with 30 mL brine, 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 n-heptane:ethyl acetate (100:0 to 60:40) to give the desired compound as white solid (65%). MS (Turbo Spray): m/z=468.2 [M+H].

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