Hydrochloric Acid → HCID 56954313, compound

Temperature

65 °C

A mixture of 5,5,5-trifluoro-4,4-dimethyl-3-oxopentanenitrile (3 g, 16:76 mmol), hydroxylamine sulfate (3.30 g, 20.11 mmol) and sodium hydrogencarbonate (3.52 g, 41.90 mmol) in a mixture of 10% methanol in water (60 mL), was heated at 65° C. for 15 h. After cooling to rt, a further 30 mL of 10% methanol in water was added, and the mixture was divided into 9×10 mL batches. Each batch was adjusted to pH 1 with concentrated hydrochloric acid and each placed into a 20 mL volume microwave vial 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 (maximum internal pressure attained was 7 bar). Each batch was cooled and neutralized with saturated aqueous sodium hydrogencarbonate solution. All processed batches were combined and concentrated in vacuo and the aqueous solution extracted with 10% isopropanol in chloroform (3×150 mL). The combined organic layers were washed with brine (200 mL), separated, dried over MgSO4 and filtered. Concentration in vacuo afforded 5-(1,1,1-trifluoro-2-methylpropan-2-yl)isoxazol-3-amine (2.34 g, 71%) as a light yellow solid which taken on without further purification. 1H NMR (300 MHz, CDCl3) δ 5.80 (s, 1H), 3.98 (brs, 2H), 1.53 (s, 6H); LC-MS (ESI) m/z 195 (M+H)+.

1. temperatureAfter cooling to rt
2. customvial fitted with a stirrer bar
3. temperatureheated
4. temperatureEach batch was cooled
5. concentrationconcentrated in vacuo
6. extractionthe aqueous solution extracted with 10% isopropanol in chloroform (3×150 mL)
7. washThe combined organic layers were washed with brine (200 mL)
8. customseparated
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationConcentration in vacuo

ORD record

ord-034550bea6ff463c909c1ab6f6106cec

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618289B2