Acetic Acid → Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate

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Reaction Steps

Sodium metal (13.8 g, 0.5 mol) was added portionwise to ice-cold anhydrous EtOH (700 mL). After complete dissolution of the Na, a mixture of 3,3-dimethylbutan-2-one (50 g, 0.5 mol) and oxalic acid diethyl ester (77 ml, 0.5 mol) was added drop-wise. The reaction mixture was stirred in ice-salt bath until TLC indicated completion of the reaction. Acetic acid (38.1 ml, 0.5 mol) was added and the mixture was stirred at RT for 30 min. The reaction mixture was cooled in an ice-salt bath and treated with hydrazine hydrate (29.4 g, 0.5 mol). After complete addition, the mixture was warmed to RT and stirred until judged complete by TLC. The reaction mixture was concentrated under reduced pressure and re-dissolved in EtOAc. The EtOAc solution was washed with NaHCO3, brine and water, dried (MgSO4) and concentrated in vacuo. The resultant solid was washed with cold petroleum ether to give ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate (49 g, 50% yield over two steps) as a white solid. 1H NMR (400 MHz, CDCl3): δ 6.65 (s, 1 H), 4.38 (q, J=6.8 Hz, 2 H), 11.39 (t, J=6.8 Hz, 3 H), 1.35 (s, 1 H); MS (ESI) m/z 197.2 (M+H+).

Provenance & Evidence