Hydrochloric Acid → 1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-amine

Temperature

100 °C

To a mixture of 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile (1 g, 5.58 mmol) in EtOH (10 mL) was added methylhydrazine (3.33 g, 28.9 mmol) and concentrated HCl (0.5 mL). Then the mixture was stirred at 100° C. for 18 h. Then the mixture was concentrated to give the residue which was distributed between DCM (20 mL) and H2O (10 mL) and extracted with DCM (20 mL×2). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated. The crude product was purified by silica column chromatography (40% EA: 60% PE, 12 g silica column). All fractions found to contain product by TLC (EA:PE=1:2, Rf=0.2) were combined and concentrated to yield a white solid of 1-methyl-3-(1,1,1-trifluoro-2-methylpropan-2-yl)-1H-pyrazol-5-amine (500 mg, 2.293 mmol, 41.1% yield): 1H NMR (400 MHz, CD3OD): δ 5.48 (s, 1H), 3.56 (s, 3H), 1.42 (s, 6H). ES-LCMS m/z 208 (M+H).

1. concentrationThen the mixture was concentrated
2. customto give the residue which
3. extractionextracted with DCM (20 mL×2)
4. washThe combined organic extracts were washed with brine (20 mL)
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by silica column chromatography (40% EA: 60% PE, 12 g silica column)
9. concentrationconcentrated

ORD record

ord-17afea3d3e984cfa89c9a4b4912ae7ce

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382238B2