1-Isopropylhydrazine → 5-amino-1-(propan-2-yl)-1H-pyrazole-4-carboxylic acid

Participants

Reaction Steps

To a solution of ethyl (2Z)-2-cyano-3-(ethyloxy)-2-propenoate (114.2 g, 0.67 mol) in ethanol (250 mL) was slowly added isopropylhydrazine (55 g, 0.74 mol) in a dropwise manner. The mixture was heated at reflux for 4 h, and then cooled to room temperature. The mixture was concentrated in vacuo. Approximately half of the crude 5-amino-1-isopropyl-1H-pyrazole-4-carboxylic acid ethyl ester (50 g) was suspended in an aqueous solution of sodium hydroxide (4M, 130 mL), and stirred with heating at reflux for 2 h. The reaction mixture was then cooled to room temperature and adjusted to pH=3.5 with concentrated HCl, wherein precipitate formation ensued. The solid was collected by filtration and dried in vacuum oven overnight to afford crude 5-amino-1-isopropyl-1H-pyrazole-4-carboxylic acid (30 g). The solid was suspended in diphenyl ether (120 mL) and stirred with heating at 160-165° C. for 2 h. The solution was then cooled to room temperature and the solvent removed in vacuo. The crude product was purified by silica gel chromatography (eluent: petroleum ether/EtOAc=1:1) to afford the product as 12 g. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.24 (d, 6H, J=6.4 Hz), 4.32 (m, 1H), 5.06 (s, 2H), 5.21 (s, 1H), 7.00 (s, 1H).

Provenance & Evidence