Acetic Anhydride → 6-(1,1-Dimethylethyl)-1H-indazole

Participants

Reaction Steps

To a solution of 5-tert-butyl-2-methylaniline (2.48 g, 15.2 mmol) in CHCl3 (40 ml) at 0° C. was slowly added acetic anhydride (3.3 ml, 34.9 mmol). The reaction mixture was warmed to room temperature and stirred for 1 h. Potassium acetate (446 mg, 4.55 mmol) was added followed by slow addition of isoamyl nitrite (4.4 ml, 32.6 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was dissolved in EtOAc and washed with water, sat'd NaHCO3 and brine then dried over MgSO4 and concentrated. The residue was dissolved in THF/MeOH (1:1, 40 mL) and 10% NaOH (4.5 mL) was added. The reaction mixture was stirred at room temperature for 10 min then neutralized with 1.0 M HCl, diluted with water and extracted with EtOAc (2×). The combined organics were washed with brine then dried over MgSO4 and concentrated. The residue was purified by silica gel chromatography with 20% to 50% EtOAc/heptane to afford 1.02 g (39%) of 6-tert-butyl-1H-indazole as an off-white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 8.03 (s, 1H), 7.70 (d, J=8.7 Hz, 1H), 7.48 (s, 1H), 7.29 (dd, J=8.7, 1.5 Hz, 1H), 1.40 (s, 9H).

Provenance & Evidence