反应详情

温度

60 °C

Aqueous barium hydroxide octahydrate solution (prepared by dissolving 55 g, 0.174 mol of barium hydroxide octahydrate in 350 mL water) was added to a solution of ethyl-2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazole carboxylate (100 g, 0.29 mol) in tetrahydrofuran (1000 mL) and denatured spirit (300 mL). The reaction mixture was stirred at a temperature of about 60° C. for about 90 minutes to about 120 minutes. After completion of reaction, the mixture was cooled to a temperature of about 45° C. and diluted with ethyl acetate and water. The pH of the reaction mixture was adjusted to 0.5-0.8 with 6N HCl at about 35° C. The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layer was treated with activated carbon (10 g) and filtered through hyflobed. The hyflobed was washed with ethyl acetate. The combined filtrate was concentrated at a temperature of about 45° C. under reduced pressure. The residue thus obtained was dissolved in a mixture of dichloromethane (400 mL) and methanol (1000 mL) and the solution was cooled to about 0° C., stirred for about 1 hour. The solid thus obtained was filtered, washed with a precooled mixture of methanol and methylene chloride, dried under reduced pressure to give febuxostat. (Yield: 81 g, 88%)

1. customAfter completion of reaction
2. temperaturethe mixture was cooled to a temperature of about 45° C.
3. customThe organic layer was separated
4. extractionthe aqueous layer was extracted with ethyl acetate
5. additionThe combined organic layer was treated with activated carbon (10 g)
6. filtrationfiltered
7. washThe hyflobed was washed with ethyl acetate
8. concentrationThe combined filtrate was concentrated at a temperature of about 45° C. under reduced pressure
9. customThe residue thus obtained
10. temperaturethe solution was cooled to about 0° C.
11. stirringstirred for about 1 hour
12. customThe solid thus obtained
13. filtrationwas filtered
14. washwashed with a precooled mixture of methanol and methylene chloride
15. customdried under reduced pressure