反应详情

温度

10 °C

To a solution of isopropyl 2-[2,4-difluoro-3-[[2-fluoro-5-(3-fluorophenyl)phenyl]methylamino]phenoxy]acetate (II(d)) (0.63 g, 1.41 mmol, 1.0 eq) in ethylene glycol (30 mL) at room temperature was added H2SO4 (0.4 mL, 7.5 mmol, 5.3 eq) dropwise. The reaction mixture was stirred overnight at 10° C. then heated at 40° C. for 3 h. The reaction was then cooled to room temperature and poured into water. The aqueous layer was extracted with EtOAc and the combined organic extracts were washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 1:5 to 1:1) to give the title compound as an oil, which crystallised on standing to give a white solid (0.54 g, 85%).

1. temperaturethen heated at 40° C. for 3 h
2. temperatureThe reaction was then cooled to room temperature
3. extractionThe aqueous layer was extracted with EtOAc
4. washthe combined organic extracts were washed with 5% Na2CO3, water and brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated in vacuo
8. customThe residue was purified by column chromatography (EtOAc:petroleum ether, 1:5 to 1:1)