Acetonitrile → HCID 117601321, compound

Temperature

0 °C

2-Chloro-4-(3,5-dimethylisoxazol-4-yl)-N-(2,2,2-trifluoroethyl)aniline (200 mg, 0.66 mmol) was dissolved in dichloromethane (10 mL) and acetonitrile (10 mL) and cooled to 0° C. under argon. To reaction mixture was added 0.5M nitronium tetrafluoroborate (1.84 ml) slowly over 20 minutes. Reaction mixture was stirred at 0° C., for 1 hour and allowed to warm to room temperature. After 3 hours, the reaction mixture was cooled to 0° C. again and 0.5M nitronium tetrafluoroborate in sulfolane (1.84 ml) was added and the reaction solution was stirred at room temperature overnight. Reaction solvents were removed under reduced pressure and the residue taken up in EtOAc and the solution was washed with aq. NaHCO3, then water, brine and dried over sodium sulfate. Solvents were removed under reduced pressure to yield a dark red oil/liquid. This material was dissolved in 2 mL of ethanol and 2 mL of acetic acid. To the solution was added Zinc dust and suspension was stirred. After 30 minutes of stirring the zinc dust was filtered off and the solvents were removed under reduced pressure. The residue was dissolved in EtOAc and the solution was washed with aq. NaHCO3, then water, brine and dried over sodium sulfate. Solvent was removed and the crude residue was purified by silica gel chromatography (Hexanes/EtOAc as the eluent) to afford 6-chloro-4-(3,5-dimethylisoxazol-4-yl)-N1-(2,2,2-trifluoroethyl)benzene-1,2-diamine as a light colored oil.

1. customTo reaction mixture
2. customReaction mixture
3. temperatureto warm to room temperature
4. waitAfter 3 hours
5. temperaturethe reaction mixture was cooled to 0° C. again
6. stirringthe reaction solution was stirred at room temperature overnight
7. customReaction solvents
8. customwere removed under reduced pressure
9. washthe solution was washed with aq. NaHCO3
10. dry with materialwater, brine and dried over sodium sulfate
11. customSolvents were removed under reduced pressure
12. customto yield a dark red oil/liquid
13. stirringwas stirred
14. filtrationwas filtered off
15. customthe solvents were removed under reduced pressure
16. dissolutionThe residue was dissolved in EtOAc
17. washthe solution was washed with aq. NaHCO3
18. dry with materialwater, brine and dried over sodium sulfate
19. customSolvent was removed
20. customthe crude residue was purified by silica gel chromatography (Hexanes/EtOAc as the eluent)

ORD record

ord-f9de2bbb2d714955b1404205439ce4ab

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09255089B2