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

Participants

Reaction Conditions

Reaction Steps

To a ice-cold solution of 13.15 g (29.1 mmol) N-benzyl-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-acetamide in 95 ml (1.659 mol) acetic acid and 199.7 ml (3.52 Mol) acetic anhydride were added in portions over 60 min. 10.04 g (145 mmol) sodium nitrite. The reaction mixture was stirred for 1 h at 0° C., 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 the pH was adjusted to 7 with solid sodium bicarbonate. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified by silica gel column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50) to give the desired compound as a light yellow solid (53%). MS (Turbo Spray): m/z=481.1 [M+H].

Provenance & Evidence