反应详情

温度

25 °C

A mixture of 179.5 g (0.72 mol) of 3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carboxylic acid ethyl ester in 880 g of ethanol 95% was stirred at 20-30° C. for 40 minutes and then treated with 78.5 g of solid sodium hydroxide. The resulting mixture was stirred for 5 h at 20-30° C. Ethanol was removed in vacuum at 45-50° C. and the residue was subsequently treated with 500 g of water at 20-30° C. to afford a clear solution. The solution was stirred for 40 minutes and filtered. To the filtrate was added 235 g of methyl tert-butyl ether and 600 g of water and the resulting mixture stirred for 20 min and then stood for 20 min. The layers were separated and the aqueous layer was acidified to pH<1 with hydrochloric acid. The crystals were filtered and washed with water to provide 147 g crude wet product. The crude wet product was suspended in 680 g of toluene and the mixture was heated at 75-85° C. for 7 h. The mixture was cooled to 20-30° C. and stirred for 1 hour at this temperature. The crystals were filtered off and dried at 50-55° C. in vacuum over night to afford 137 g (86% yield) of the title acid as a white to slightly yellow solid with a purity of 99.9% (HPLC).

1. stirringThe resulting mixture was stirred for 5 h at 20-30° C
2. customEthanol was removed in vacuum at 45-50° C.
3. additionthe residue was subsequently treated with 500 g of water at 20-30° C.
4. customto afford a clear solution
5. stirringThe solution was stirred for 40 minutes
6. filtrationfiltered
7. additionTo the filtrate was added 235 g of methyl tert-butyl ether and 600 g of water
8. stirringthe resulting mixture stirred for 20 min
9. waitstood for 20 min
10. customThe layers were separated
11. filtrationThe crystals were filtered
12. washwashed with water
13. customto provide 147 g crude wet product
14. temperaturethe mixture was heated at 75-85° C. for 7 h
15. temperatureThe mixture was cooled to 20-30° C.
16. stirringstirred for 1 hour at this temperature
17. filtrationThe crystals were filtered off
18. customdried at 50-55° C. in vacuum over night