Hydrochloric Acid → 5-(1-(Trifluoromethyl)cyclopropyl)isoxazol-3-amine

Temperature

65 °C

A mixture of 3-oxo-3-(1-(trifluoromethyl)cyclopropyl)propanenitrile (1 g, 5.65 mmol) (prepared as described in example 137A step 1), hydroxylamine sulfate (1.11 g, 6.78 mmol) and sodium hydrogencarbonate (1.2 g, 14.13 mmol) in a mixture of 10% methanol in water (20 mL), was heated at 65° C. for 15 h. After cooling to rt, the mixture was adjusted to pH 1 with concentrated hydrochloric acid and separated into two equal 10 mL batches and placed into two separate 20 mL microwave vials fitted with a stirrer bar. After sealing, each batch was placed in a Biotage Microwave Synthesizer and heated (with stirring) at 140° C. for 5 min. Each batch was cooled and neutralized with saturated aqueous sodium hydrogencarbonate solution. Both processed batches were combined and concentrated in vacuo and the aqueous solution extracted, twice, with dichloromethane. The combined organic layers were washed with brine, separated, dried over MgSO4 and filtered. Concentration in vacuo afforded 5-(1-(trifluoromethyl)cyclopropyl)isoxazol-3-amine (687 mg, 64%) as a light yellow solid which taken on without further purification. LC-MS (ESI) m/z 193 (M+H)+.

1. temperatureAfter cooling to rt
2. customseparated into two equal 10 mL batches
3. customseparate 20 mL microwave vials
4. customfitted with a stirrer bar
5. temperatureheated
6. temperatureEach batch was cooled
7. concentrationconcentrated in vacuo
8. extractionthe aqueous solution extracted
9. washThe combined organic layers were washed with brine
10. customseparated
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationConcentration in vacuo

ORD record

ord-17cc6dc13b2540fbaf5d750cbde10281

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09320739B2