Potassium Carbonate → 4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethylsulfanyl}-benzoic acid methyl ester

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Reaction Steps

To a solution of 74 mg (0.44 mmol) methyl 4-mercaptobenzoate in 3 ml N,N-dimethylformamide was added 61 mg (0.44 mmol) potassium carbonate at 0° C. The reaction mixture was stirred for 15 min. and then 200 mg (0.44 mmol) 1-(2-bromo-1-cyclohexyl-ethyl)-2-(4-chloro-phenyl)-5,6-difluoro-1H-benzoimidazole (Example 34, intermediate) was added at the same temperature. The cooling bath was removed and the reaction mixture stirred for 18 hours at room temperature. The reaction mixture was poured on 10% aqueous 30 ml citric acid and 30 ml ethyl acetate and the layers were separated. The aqueous layer was extracted a second time with 30 ml ethyl acetate. The combined organic layers were washed with 30 ml brine, dried over magnesium sulfate, filtered and concentrated under vacuum. 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 70:30) to give the desired compound as a colorless solid (65%). MS (Turbo Spray) m/z=541.2 [M+H].

Provenance & Evidence