反应详情

Add n-butyllithium (1.6 M in hexanes, 4.5 mL, 7.4 mmol) dropwise to a mixture of zirconocene dichloride (1.05 g, 3.6 mmol) in dry THF (15 mL) at −78° C. and stir for 1 h. Add a solution of toluene-4-sulfonic acid 2,2-difluorovinyl ester (420 mg, 1.8 mmol) in THF (3.6 mL) dropwise. Stir at −78° C. for 5 min and at room temperature for 3 h. Add triphenyl phosphine (79 mg, 0.3 mmol) and tris(dibenzylidineacetone)dipalladium(0) (34 mg, 0.036 mmol), stir for 10 min, add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (722 mg, 2.0 mmol) and zinc iodide (1.35 g, 4.3 mmol). Reflux the reaction for 1 h and stir at room temperature overnight. Add pH=7 phosphate buffer (400 mL) and ethyl acetate (250 mL). Separate the layers and wash with saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (2×100 mL), dry (magnesium sulfate), concentrate and purify (silica gel chromatography, eluting with 25:75 ethyl acetate:hexanes) to give the title compound (187 mg, 35%).

1. stirringStir at −78° C. for 5 min and at room temperature for 3 h
2. temperatureReflux
3. customthe reaction for 1 h
4. stirringstir at room temperature overnight
5. customSeparate the layers
6. washwash with saturated aqueous ammonium chloride (2×100 mL), saturated aqueous sodium bicarbonate (2×100 mL)
7. dry with materialdry (magnesium sulfate)
8. concentrationconcentrate
9. custompurify
10. wash(silica gel chromatography, eluting with 25:75 ethyl acetate:hexanes)