反应详情

温度

25 °C

A solution of 1-methoxy-3-methoxymethoxy benzene (3.62 g., 21.55 mmole), prepared as described in J. Med. Chem. 1995, 38, 1437-1445, in THF (15 mL) at −30° C. was treated with n-butyllithium (8.28 ml. of 2.5M in hexane, 20.69 mmole), stirred for 1 hour at 25° C., cooled to 0° C., treated with anhydrous zinc chloride beads (3.5 g, 25.67 mmole), stirred for 2 hours at 25° C., treated with a solution of methyl-2-bromo-5-nitrobenzoate (5.0 g, 19.23 mmol) in THF (20 mL) and bis(triphenylphosphine)palladium dichloride (600 mg), stirred it 65° C. for 15 hours, cooled, and treated with chloroform and aqueous KHCO3. The precipitated zinc salts were filtered, and the water layer was removed, and the organic layer dried over (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 8% ethyl acetate in dichloromethane to provide the desired product. MS (ESI(−)Q1MS) m/z 346 (M−H)−.

1. temperaturecooled to 0° C.
2. stirringstirred for 2 hours at 25° C.
3. stirringstirred it 65° C. for 15 hours
4. temperaturecooled
5. filtrationThe precipitated zinc salts were filtered
6. customthe water layer was removed
7. dry with materialthe organic layer dried over (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe concentrate was purified by flash column chromatography on silica gel with 8% ethyl acetate in dichloromethane