反应详情

温度

90 °C

Add 4-bromo-butyric acid methyl ester (74.30 g, 410.46 mmol) to a mixture of 5-ethyl-2-isopropoxycarbonylamino-4-trifluoromethyl-benzoic acid methyl ester (39.05 g, 117.16 mmol) and cesium carbonate (114.65 g, 351.88 mmol) in N,N-dimethylformamide (800 mL). Heat the mixture at 90° C. for 4 h and the allow it to cool to room temperature. Filter the mixture through Celite then dilute the mixture with water (2 L) and ethyl acetate (2 L). Wash the organic layer with water (500 mL) and brine (500 mL). Dry the organic layer over anhydrous sodium sulfate and filter. Remove the solvents under reduced pressure and purify the resulting residue by column chromatography on silica gel, eluting with ethyl acetate/hexanes (0 to 15%), to provide the title compound as a white solid (39.75 g, 78%): TLC Rf 0.42 (3:1 hexanes/ethyl acetate); 1H NMR (CDCl3, 300 MHz) δ 1.0-1.10 (m, 3H), 1.22-1.32 (m, 6H), 1.78-1.89 (m, 2H), 2.37-2.40 (m, 2H), 2.82-2.89 (m, 2H), 3.41-3.80 (m, 5H), 3.89 (s, 3H), 4.78-5.02 (m, 1H), 7.43 (s, 1H), 7.91 (s, 1H).

1. temperatureto cool to room temperature
2. filtrationFilter the mixture through Celite
3. additionthen dilute the mixture with water (2 L) and ethyl acetate (2 L)
4. washWash the organic layer with water (500 mL) and brine (500 mL)
5. dry with materialDry the organic layer over anhydrous sodium sulfate
6. filtrationfilter
7. customRemove the solvents under reduced pressure
8. custompurify the resulting residue by column chromatography on silica gel
9. washeluting with ethyl acetate/hexanes (0 to 15%)