Sodium Hydroxide → 3-(1,3-Difluoro-2-methylpropan-2-yl)isoxazol-5-amine

Temperature

100 °C

To a solution of 5-fluoro-4-(fluoromethyl)-4-methyl-3-oxopentanenitrile (1.00 g, 6.2 mmol) and NaOH (0.272 g, 6.8 mmol) in EtOH (5 mL) and water (5 mL) at room temperature was added a solution of hydroxylamine sulfate (1.12 g, 6.8 mmol) in water (5 mL). To the mixture was added additional NaOH until the pH was about 8. After heating at 100° C. for 2 hours, it was quenched with water and extracted with CH2Cl2. Extracts were washed with water, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluted with gradient of 0-50% EtOAc/hexane to afford 3-(1,3-difluoro-2-methylpropan-2-yl)isoxazol-5-amine as a solid (0.191 g, 17%). 1H NMR (300 MHz, CDCl3) δ 5.16 (s, 1H), 4.63 (q, 2H), 4.5 (q and br, 4H), 1.37 (s, 3H); LC-MS (ESI) m/z 177 (M+H)+.

1. customit was quenched with water
2. extractionextracted with CH2Cl2
3. washExtracts were washed with water
4. dry with materialdried over MgSO4
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel chromatography
7. washeluted with gradient of 0-50% EtOAc/hexane

ORD record

ord-1a6734c638a44c348162d7564808c180

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618289B2