反应详情

温度

50 °C

In a 3-necked 5-L round-bottomed flask, equipped with a mechanical stirrer and thermocouple, was suspended 5-chloro-α-fluoro-2-methoxy-α-[2-nitro-4-(trifluoromethyl)phenyl]benzeneacetic acid, methyl ester (450 g, 1.067 mol) in methanol (2.0 L) and 1.0 N aqueous sodium hydroxide (1.10 L, 1.10 mol). The reaction mixture was stirred for 4.5 hours at about 50° C. to complete the hydrolysis (determined by HPLC analysis). The reaction mixture was cooled to room temperature and concentrated on a rotary evaporator to remove most of the methanol. The residue was partitioned between tert-butylmethylether/hexane (1.2 L/0.5L) and water (1.4 L) and extracted. The organic layer was back-extracted with water (500 mL). The combined aqueous layers were cooled in an ice bath and while stirring vigorously, acidified with concentrated hydrochloric acid to about pH 1 (about 110 mL). Preferably, seed crystals of the title compound were added resulting in crystallization/precipitation of the product. The material was filtered after stirring for 3 hours at 0° C., air and vacuum dried overnight to afford 418.1 g of the title compound (96% yield when corrected for solvent, 99.6% by HPLC). A sample was recrystallized from toluene/hexane (1:1.25 at about 5 mL/g) to afford pure title compound.

1. customIn a 3-necked 5-L round-bottomed flask, equipped with a mechanical stirrer
2. customthe hydrolysis (determined by HPLC analysis)
3. temperatureThe reaction mixture was cooled to room temperature
4. concentrationconcentrated on a rotary evaporator
5. customto remove most of the methanol
6. customThe residue was partitioned between tert-butylmethylether/hexane (1.2 L/0.5L) and water (1.4 L)
7. extractionextracted
8. extractionThe organic layer was back-extracted with water (500 mL)
9. temperatureThe combined aqueous layers were cooled in an ice bath
10. stirringwhile stirring vigorously
11. additionPreferably, seed crystals of the title compound were added
12. customresulting in crystallization/precipitation of the product
13. filtrationThe material was filtered
14. stirringafter stirring for 3 hours at 0° C.
15. customair and vacuum dried overnight