反应详情

温度

0 °C

2-Fluorobenzoic acid (6 g, 42.8 mmole) was dissolved in 300 mL of anhydrous THF and the resulting reaction solution was cooled to 0° C. To this solution was added sodium hydride (1.88 g of a 60% oil dispersion, 47.1 mmole). The reaction mixture was allowed to warm to room temperature over 1 h. The THF was removed by evaporation before addition of 2-chloro-3-oxo-3-phenyl-propionic acid ethyl ester (9.7 g, 42.8 mmole) in 250 mL of ethanol. Reaction solution was warmed at reflux for 24 h. The ethanol was removed by evaporation and the resulting product was dissolved in water and extracted with toluene. The toluene was washed with 2 N aqueous Na2CO3, and saturated NaCl. The resulting toluene layer was concentrated and purified by chromatography (5-8% ethyl acetate in hexanes gradient) providing 2-fluoro-benzoic acid 1-ethoxycarbonyl-2-oxo-2-phenyl-ethyl ester (Intermediate XVIIb, 5.3 g, 38% yield)

1. customthe resulting reaction solution
2. temperatureto warm to room temperature over 1 h
3. customReaction solution
4. temperaturewas warmed
5. temperatureat reflux for 24 h
6. customThe ethanol was removed by evaporation
7. dissolutionthe resulting product was dissolved in water
8. extractionextracted with toluene
9. washThe toluene was washed with 2 N aqueous Na2CO3, and saturated NaCl
10. concentrationThe resulting toluene layer was concentrated
11. custompurified by chromatography (5-8% ethyl acetate in hexanes gradient)