Acetic Acid → 3-tert-Butyl-1-(2-methylphenyl)-1H-pyrazol-5-amine

Participants

Reaction Steps

4,4-Dimethyl-3-oxopentanenitrile (36.7 g, 0.29 mol), (2-methylphenyl)hydrazine hydrochloride (47.7 g, 0.29 mol), and glacial acetic acid (7.03 g, 6.7 mL, 0.12 mol) were dissolved in abs ethanol (585 mL) and heated under reflux for 18 h. After removal of the solvent under reduced pressure, EtOAc and water (500 mL each) were added, then sodium bicarbonate (42 g, 0.50 mol) was carefully added. After addition of hexane (500 mL), the organic phase was separated, washed with brine (500 mL), and dried over Na2SO4. The mixture was then filtered through a pad of silica gel (500 g) on a sintered glass funnel. The pad was eluted with hexanes/EtOAc (1:1, v/v), and the filtrate was concentrated under reduced pressure. The resulting solid was triturated with hexanes/EtOAc (9:1, v/v), filtered, washed and dried in vacuo to afford a colorless solid (61.5 g, 93%). 1H NMR (400 MHz, CD2Cl2) δ 1.29 (s, 9H), 2.12 (s, 3H), 3.56 (br, 2H), 5.48 (s, 1H), 7.28 (m, 2H), 7.31 (m, 2H).

Provenance & Evidence