反应详情

温度

90 °C

2-Hydroxy-3-methoxybenzoic acid (15.66 g, 93 mmol), DMF (200 ml), potassium carbonate (51.4 g, 372 mmol) and pentyl bromide (29 ml, 233 mmol) were mixed, and this solution was stirred at 90° C. for 1 hour. DMF was evaporated under reduced pressure, and water (100 ml) was added. The aqueous layer was extracted 3 times with ethyl acetate (150 ml). The organic layers were combined, washed twice with saturated brine (70 ml), and dried over anhydrous magnesium sulfate. The drying agent was filtered off and the filtrate was concentrated under reduced pressure. To the obtained residue were added a 1N aqueous sodium hydroxide solution (70 ml) and ethanol (70 ml), and the mixture was refluxed under heating for 1 hour. A 1N aqueous sodium hydroxide solution (70 ml) and ethanol (70 ml) were further added, and the mixture was refluxed under heating for 2 hours. Ethanol was evaporated under reduced pressure, and conc. hydrochloric acid was added to make this solution acidic. The aqueous layer was extracted 3 times with ethyl acetate (100 ml). The organic layers were combined, washed twice with saturated brine (100 ml), and dried over anhydrous magnesium sulfate. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=2/1-1/1) to give 3-methoxy-2-pentyloxybenzoic acid (20.5 g, 97%) as a pale-yellow oil.

1. customDMF was evaporated under reduced pressure, and water (100 ml)
2. additionwas added
3. extractionThe aqueous layer was extracted 3 times with ethyl acetate (150 ml)
4. washwashed twice with saturated brine (70 ml)
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationThe drying agent was filtered off
7. concentrationthe filtrate was concentrated under reduced pressure
8. additionTo the obtained residue were added a 1N aqueous sodium hydroxide solution (70 ml) and ethanol (70 ml)
9. temperaturethe mixture was refluxed
10. temperatureunder heating for 1 hour
11. additionA 1N aqueous sodium hydroxide solution (70 ml) and ethanol (70 ml) were further added
12. temperaturethe mixture was refluxed
13. temperatureunder heating for 2 hours
14. customEthanol was evaporated under reduced pressure, and conc. hydrochloric acid
15. additionwas added
16. extractionThe aqueous layer was extracted 3 times with ethyl acetate (100 ml)
17. washwashed twice with saturated brine (100 ml)
18. dry with materialdried over anhydrous magnesium sulfate
19. filtrationThe drying agent was filtered off
20. concentrationthe filtrate was concentrated under reduced pressure
21. customThe obtained residue was purified by column chromatography (hexane/ethyl acetate=2/1-1/1)