Hydrochloric Acid → N-(1-(2,4-difluorophenyl)-1H-pyrazol-5-yl)acetamide

Temperatur

80 °C

A solution of 1-(2,4-difluorophenyl)-1H-pyrazol-5-amine (5.00 g, 26 mmol), in 80 mL of 1,2-DCE was added DMAP (0.94 g, 7.7 mmol), Ac2O (12 mL, 128 mmol) and Et3N (18 mL, 128 mmol). The dark brown reaction mixture was heated at 80° C. in an oil bath for 18 h. After cooling to RT, it was diluted with 20 mL of DCM and washed with saturated aqueous solution of sodium bicarbonate, and brine. The resulting organic solution was then dried over magnesium sulfate and concentrated under reduced pressure to give viscous brown oil which contains the bis-acylated product along with residual amount of Ac2O and AcOH. The viscous brown oil was dissolved in 50 mL of EtOH and treated with KOH (5.0 g 129 mmol). After the reaction mixture was stirred at RT for 4 h, it was acidified with 2 N HCl to pH 4. The volatile portion was removed on the rotovap. The residue was diluted with 150 mL of EtOAc, washed with saturated aqueous solution of sodium bicarbonate, and brine. The resulting organic solution was then dried over magnesium sulfate and concentrated under reduced pressure. Purification of the crude material on an ISCO 80 g column (60-100% EtOAc in hexanes) afforded N-(1-(2,4-difluorophenyl)-1H-pyrazol-5-yl)acetamide as an off-white solid. MS (ES+): 238.1 (M+H)+.

1. temperatureAfter cooling to RT
2. washwashed with saturated aqueous solution of sodium bicarbonate, and brine
3. dry with materialThe resulting organic solution was then dried over magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. customto give viscous brown oil which
6. customThe volatile portion was removed on the rotovap
7. additionThe residue was diluted with 150 mL of EtOAc
8. washwashed with saturated aqueous solution of sodium bicarbonate, and brine
9. dry with materialThe resulting organic solution was then dried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customPurification of the crude material on an ISCO 80 g column (60-100% EtOAc in hexanes)

ORD-Eintrag

ord-e76ac1841d114f8aabc2b15d1f452ecb

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367671B2