Triethylamine → 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole

Temperature

0 °C

To a mixture of sodium hypochlorite (23 mL), triethylamine (Preparation 62E, 0.021 mL, 0.155 mmol), and dichloromethane (1.0 mL) at 0° C. was added dropwise a solution of (E)-4-bromo-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-ynyloxy)benzaldehyde oxime (0.036 g, 0.077 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at 0° C. for 30 min. and then at room temperature for 1.5 h. The reaction mixture was diluted with dichloromethane, and the organic layer was collected. The aqueous layer was extracted with dichloromethane (2×), and the combined organic layers were washed with brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by trituration with methanol with sonication afforded 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole (0.026 g, 0.056 mmol, 73% yield) as a white solid. The product had an HPLC ret. time=3.91 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=464.9. 1H NMR (500 MHz, CDCl3) δ ppm 5.49 (s, 2H), 7.23-7.27 (m, 2H), 7.55-7.59 (m, 2H), 7.60-7.65 (m, 1H), 7.73 (d, J=7.49 Hz, 2H), and 7.78 (d, J=8.05 Hz, 1H).

1. waitat room temperature for 1.5 h
2. customthe organic layer was collected
3. extractionThe aqueous layer was extracted with dichloromethane (2×)
4. washthe combined organic layers were washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationConcentration under reduced pressure
7. customfollowed by trituration with methanol with sonication

ORD record

ord-045fe5c332984e42a83c0d4e2d919d05

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09216972B2