反应详情

Diisopropylethylamine (435 μl, 2.5 mmol) was added to a dichloromethane (10 ml) solution of 4-amino-6-fluoro-5-hydroxy-2-methyl-biphenyl-3-carbonitrile (I-41) (353 mg, 1.46 mmol), then after cooling with ice, O-acetylsalicyloyl chloride (318 mg, 1.6 mmol) was added, followed by stirring at the same temperature for 30 minutes. With cooling with ice, water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, then the solvent was evaporated away under reduced pressure. In xylene (30 ml) and in the presence of a catalytic amount of p-tosylic acid, the resulting residue was heated under reflux for 2 hours with a Dean-Stark device. After cooling, the solvent was evaporated away, and the resulting residue was dissolved in chloroform, washed with saturated sodium bicarbonate water, then dried over anhydrous sodium sulfate, and the solvent was evaporated away under reduced pressure. The resulting residue was washed with a mixed solvent of isopropyl ether and ethanol, and the solid was collected by nitration to obtain the entitled compound (320 mg, 64%) as a pale yellow solid.

1. additionwas added
2. additionwas added
3. extractionfollowed by extraction with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was evaporated away under reduced pressure
7. temperatureIn xylene (30 ml) and in the presence of a catalytic amount of p-tosylic acid, the resulting residue was heated
8. temperatureunder reflux for 2 hours with a Dean-Stark device
9. temperatureAfter cooling
10. customthe solvent was evaporated away
11. dissolutionthe resulting residue was dissolved in chloroform
12. washwashed with saturated sodium bicarbonate water
13. dry with materialdried over anhydrous sodium sulfate
14. customthe solvent was evaporated away under reduced pressure
15. washThe resulting residue was washed with a mixed solvent of isopropyl ether and ethanol
16. customthe solid was collected by nitration