Acetic Anhydride → 1-Acetyl-5-(acetoxymethyl)indazole

Participants

Reaction Conditions

Reaction Steps

To a suspension of 2-methyl-4-(hydroxymethyl)aniline (compound 105, 4.0 g, 29 mmol) and potassium acetate (Aldrich, 8.6 g, 88 mmol) in chloroform (Calbiochem, 60 mL), was added acetic anhydride (Aldrich, 8.3 mL, 88 mmol) at room temperature, and the temperature was allowed to increase to 45° C. The mixture was then heated to reflux temperature for 2 hours under nitrogen. After cooling to room temperature, isoamylnitrite (Aldrich, 7.8 mL, 88 mmol) and 18-crown-6 (Aldrich, 1.5 g, 0.6 mmol) were added. The reaction mixture was heated at its reflux temperature for 28 hours. After returning to room temperature, the mixture was further treated with acetic anhydride (10 mL) and the solution was stirred at room temperature for 12 hours. The reaction mixture was diluted with methylene chloride (600 mL) and washed with saturated aqueous NaHCO3 aqueous solution (300 mL), water (300 mL) and brine (50 mL). After drying (Na2SO4), the organic solvent was removed under vacuum to give a yellow oil which was purified by flash chromatography on silica gel (85:15 hexane-ethyl acetate) to yield the title compound (106, 6.21 g, 91%). TLC Rf 0.45 (70:30 hexane-ethyl acetate); MS (electrospray) 233 (M+1); 1H N MR (CDCl3) δ 2.12 (s, 3H), 2.79 (app d, 3H, J=0.4 Hz), 5.23 (s, 2H), 7.56 (dd, 1H, J=8.8, 1.6 Hz), 7.74 (t, 1H, J=0.8 Hz), 8.12 (s, 1H), 8.43 (dd, 1H, J=8.8, 0.6 Hz).

Provenance & Evidence