Water → Cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid methyl ester

Participants

Reaction Steps

To a solution of 5.86 g (13.58 mmol) cyclohexyl-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-acetic acid in 60 ml N,N-dimethylformamide was added 652 mg (14.94 mmol) sodium hydride (55% dispersion in mineral oil) and 2.02 g (14.26 mmol) methyl iodide. The reaction mixture was poured on 300 ml water and 300 ml ethyl acetate and the phases were separated. The aqueous layer was extracted a second time with 300 ml ethyl acetate. The combined organic layers were washed twice with 300 ml water and once with 300 ml brine, dried over magnesium sulfate, filtered and concentrated. 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). Light yellow solid (88%). MS (Turbo Spray) m/z=446.3 [M+H].

Provenance & Evidence