反应详情

A solution of methyl 5-bromo-2-chloro-4-hydroxybenzoate (Preparation 51, 2.5 g, 9.42 mmol) and lithium hydroxide monohydrate (395 mg, 9.42 mmol) in THF (10 mL) was stirred at room temperature for 10 minutes. Dimethyl sulphate (0.45 mL, 4.71 mmol) was added dropwise and left to stir at room temperature for 45 minutes before heating to 75° C. for 3 hours. Additional dimethyl sulphate (0.45 mL, 4.71 mmol) was added dropwise and the reaction stirred at 75° C. for 16 hours. The reaction was cooled to room temperature, diluted with EtOAc (20 mL), washed with brine (30 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting from 5-10% EtOAc in heptanes to afford the title compound as a white solid (1.70 g, 65%).

1. waitleft
2. temperaturebefore heating to 75° C. for 3 hours
3. stirringthe reaction stirred at 75° C. for 16 hours
4. temperatureThe reaction was cooled to room temperature
5. washwashed with brine (30 mL)
6. dry with materialdried over magnesium sulphate
7. concentrationconcentrated in vacuo
8. customThe residue was purified by silica gel column chromatography
9. washeluting from 5-10% EtOAc in heptanes