3,5-Dimethyl-4-hydroxybenzonitrile → 4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-3,5-dimethyl-benzonitrile

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To an ice-cold solution of 0.38 g (0.97 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c), 0.157 g (1.07 mmol) 3,5-dimethyl-4-hydroxybenzonitrile (commercially available) and 0.29 ml (1.17 mmol) tri-N-butylposphine in 8 ml tetrahydrofuran, 0.20 g (1.17 mmol) N′N′N′N-tetramethylazodicarboxylate were added in one portion. After 48 h stirring at RT another 0.29 ml (1.17 mmol) tri-N-butylposphine and 0.2 g (1.17 mmol) N′N′N′N-tetramethylazodicarboxylate were added. The reaction mixture was stirred at RT for another 5 days, silica gel was added and the suspension evaporated to dryness. The residue was chromatographed three times using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane and tert-butyl methyl ether (100:0 to 60:40) to give the desired compound as a light yellow solid (22%). MS (Turbo Spray): m/z=520.3 [M+H].

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