Pinacolone → 5-tert-Butyl-1-(4-methanesulfonyl-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester

Participants

Reaction Steps

To a solution of 1M NaHMDS in THF in 120 mL of THF was added dropwise pinacolin (3.1 mL, 25 mmol) at 78° C. After 1 hour, diethyl oxalate (3.7 mL, 27.5 mmol) was added dropwise. The reaction mixture was allowed to warm up to room temperature and stirred overnight. The reaction was quenched by adding 1N HCl solution (50 mL). The reaction mixture was extracted with EtOAc and dried with MgSO4. The mixture was concentrated in vacuo. The product 2h was used without further purification. To a solution of 2h (1 g, 5 mmol) in EtOH (50 mL) was added 4-methylsulfonylphenylhydrazine 1a (1.22 g, 5.5 mmol) at room temperature. The reaction mixture was stirred overnight and refluxed for 3 hour. After cooling, the solvent was removed in vacuo. The resulting solid was purified by column chromatography with hexanes/EtOAc (1:1) to afford the titled compound (1 g, 57% yield) as a white solid. mp 174.9-177.6° C. 1H NMR (300 MHz, DMSO-d6): δ 8.11 (d, J=9 Hz, 2H), 7.80 (d, J=9 Hz, 2H), 6.76 (s, 1H), 4.27 (q, J=7 Hz, 2H), 3.35 (s, 3H), 1.27 (t, J=7 Hz, 3H), 1.16 (s, 9H).

Provenance & Evidence