反应详情

A mixture of methyl 3-bromo-2-hydroxy-6-methylbenzoate (Intermediate 44, 114.5 g), dimethyl sulfate (61 mL) and potassium carbonate (166 g) in acetone (11) was heated at reflux for 2.5 hours. After cooling, the mixture was filtered and the filtrate was evaporated to dryness. The residue was dissolved in DCM and washed with water, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-40%. The product was purified again by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%. The product was again purified by chromatography on silica, eluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10% to give methyl 3-bromo-2-methoxy-6-methylbenzoate (66 g).

1. temperaturewas heated
2. temperatureat reflux for 2.5 hours
3. temperatureAfter cooling
4. filtrationthe mixture was filtered
5. customthe filtrate was evaporated to dryness
6. dissolutionThe residue was dissolved in DCM
7. washwashed with water
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customThe filtrate was evaporated to dryness
11. customthe residue was purified by chromatography on silica
12. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-40%
13. customThe product was purified again by chromatography on silica
14. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%
15. customThe product was again purified by chromatography on silica
16. washeluting with a mixture of tert-butyl methyl ether and pentane with a gradient of 0-10%