Phenylhydrazine hydrochloride → 3-(1,1-difluoroethyl)-1-phenyl-1H-pyrazol-5-amine

Temperature

70 °C

A stirred mixture of 4,4-difluoro-3-oxopentanenitrile (prepared as described in Example 152A Step 1) (1 g, 7.52 mmol) and phenyl hydrazine hydrochloride (1.08 g, 7.52 mmol) in ethanol (30 mL) was heated at 70° C. for 8 h. After cooling to rt, the mixture was concentrated under reduced pressure. The residue was partitioned between dichloromethane (200 mL) and saturated aqueous sodium hydrogen carbonate solution (200 mL). The organic layer was separated and dried over magnesium sulfate and filtered. Concentration under reduced pressure gave an oil, which was purified via silica gel column chromatography (eluting with a gradient of 5% to 65% ethyl acetate in hexanes) to afford 3-(1,1-difluoroethyl)-1-phenyl-1H-pyrazol-5-amine (528 mg, 31%) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.36-7.57 (m, 5H), 5.81 (s, 1H), 3.84 (brs, 2H), 2.01 (t, J=18 Hz, 3H); LC-MS (ESI) m/z 224 (M+H)+.

1. temperatureAfter cooling to rt
2. concentrationthe mixture was concentrated under reduced pressure
3. customThe residue was partitioned between dichloromethane (200 mL) and saturated aqueous sodium hydrogen carbonate solution (200 mL)
4. customThe organic layer was separated
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationConcentration under reduced pressure
8. customgave an oil, which
9. customwas purified via silica gel column chromatography (
10. washeluting with a gradient of 5% to 65% ethyl acetate in hexanes)

ORD record

ord-dc6c821a1abe4ebdb5a73e1621d03574

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618289B2