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

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).

1. customThe reaction was quenched
2. additionby adding 1N HCl solution (50 mL)
3. extractionThe reaction mixture was extracted with EtOAc
4. dry with materialdried with MgSO4
5. concentrationThe mixture was concentrated in vacuo
6. customThe product 2h was used without further purification
7. stirringThe reaction mixture was stirred overnight
8. temperaturerefluxed for 3 hour
9. temperatureAfter cooling
10. customthe solvent was removed in vacuo
11. customThe resulting solid was purified by column chromatography with hexanes/EtOAc (1:1)

ORD record

ord-f6a56d8d4be1467b83ca038eeb0a6c16

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096532B2