Hydrochloric Acid → 5-(1-Methoxy-2-methylpropan-2-yl)-1,2-oxazol-3-amine

To a mixture of 5-methoxy-4,4-dimethyl-3-oxopentanenitrile (1 g, 6.5 mmol) in ethanol (100 mL), was added 96% sodium hydroxide (308 mg, 7.70 mmol). To this was added a solution of hydroxylamine hydrochloride (537 mg, 7.70 mmol) in water (100 mL). The resulting solution (pH 7.8) was stirred at 60° C. for 22 h, then cooled to room temperature. To this was added concentrated hydrochloric acid (3 mL, 36 mmol) and the mixture refluxed (80° C.) for 1 h. The reaction mixture was concentrated under reduced pressure to remove ethanol and the residue was mixed with 30% sodium hydroxide (2.1 g). The mixture was shaken with chloroform. The chloroform layer was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give an oil. Purification via silica gel chromatography afforded 5-(1-methoxy-2-methylpropan-2-yl)isoxazol-3-amine as a colorless solid (350 mg, 32%). 1H NMR (300 MHz, CDCl3) δ 5.60 (s, 1H), 3.39 (s, 2H), 3.32 (s, 3H), 2.94 (brs, 2H), 1.28 (s, 6H); LC-MS (ESI) m/z 171 (M+H)+.

1. temperaturethe mixture refluxed (80° C.) for 1 h
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customto remove ethanol
4. additionthe residue was mixed with 30% sodium hydroxide (2.1 g)
5. washThe chloroform layer was washed with water
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customto give an oil
9. customPurification via silica gel chromatography

ORD record

ord-b3dcb10bb3664f2ebfe9387cddb5e46c

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969587B2