反应详情

温度

70 °C

Methyl 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoate was dissolved in isopropanol (20 mL), and 1 mol/L aqueous sodium hydroxide solution (30 mL) was added. The mixture was stirred at 70° C. for 3 h, and completion of the reaction was confirmed by HPLC. After cooling the reaction mixture to room temperature, activated carbon (Sirasagi A) (1.0 g) was added. After stirring, the mixture was filtered using powder cellulose (KC FLOCK). The reaction container and the filter were washed with isopropanol (5 mL)/water (5 mL) solution, and combined with the filtrate. Water (20 mL) and hexane (20 mL) were added to the obtained filtrate and, after stirring, the organic layer was removed. The aqueous layer was washed again with hexane (20 mL). The aqueous layer was ice-cooled, methylisopropylketone (50 mL) was added while adding 2 mol/L hydrochloric acid solution (10 mL) dropwise at 10° C. After the addition, the mixture was stirred at room temperature and the aqueous layer was discarded. The organic layer was washed twice with 10% brine (20 mL). After washing, the solvent was evaporated under reduced pressure to give 5-(3-chloro-2-fluorobenzyl)-2,4-dimethoxybenzoic acid (4.8 g, yield 81%, from methyl 5-bromo-2,4-dimethoxybenzoate obtained in Step 2).

1. temperatureAfter cooling the reaction mixture to room temperature
2. additionactivated carbon (Sirasagi A) (1.0 g) was added
3. stirringAfter stirring
4. filtrationthe mixture was filtered
5. washThe reaction container and the filter were washed with isopropanol (5 mL)/water (5 mL) solution
6. additionWater (20 mL) and hexane (20 mL) were added to the obtained filtrate
7. stirringafter stirring
8. customthe organic layer was removed
9. washThe aqueous layer was washed again with hexane (20 mL)
10. temperaturecooled
11. additionmethylisopropylketone (50 mL) was added
12. additionwhile adding 2 mol/L hydrochloric acid solution (10 mL) dropwise at 10° C
13. additionAfter the addition
14. stirringthe mixture was stirred at room temperature
15. washThe organic layer was washed twice with 10% brine (20 mL)
16. washAfter washing
17. customthe solvent was evaporated under reduced pressure