Acetic Acid → N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide

To a ice-cold solution of 9.50 g (19.79 mmol) N-benzyl-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide in 64.53 ml (1128 mmol) acetic acid and 135.84 ml (2395 mmol) acetic anhydride were added in portions over 60 min. 6.83 g (99 mmol) sodium nitrite. The reaction mixture was stirred for 1 h in an ice-bath, then at room temperature overnight. The mixture was evaporated and the residue was taken up in saturated aqueous sodium bicarbonate solution and ethyl acetate and solid sodium bicarbonate was added to adjust the pH to 7. The aqueous layer was extracted twice with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The remaining brown foam was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane and ethyl acetate (100:0 to 50:50). Yellow solid (72%). MS (Turbo Spray): m/z=509.2 [M+H].