反应详情

温度

4.5 °C

In a four neck flask having a capacity of 200 ml, 4′-cyano-3-(4-fluorophenylthio)2-hydroxy-2-methyl-3′-trifluoromethylpropionanilide (12.2 g, 30.6 mmol) produced by a method described in EP1462442-A and ethyl acetate (20 ml) were sequentially added, and then agitated under an ice cooling (2 to 7° C.). Ethyl acetate solution of monoperphthalic acid (166.58 g, net amount 22.31 g, 122.5 mmol) was added dropwise at a temperature of 10° C. or less, and then agitated for 1 hour. 20% Potassium hydroxide solution (117.5 g) was added dropwise and then subjected to a phase separation. The water layer was extracted with ethyl acetate (30 ml), and the organic layers were combined, and the combined organic layer was washed with an aqueous solution dissolving 3.0 g of sodium pyrosulfite in de-ionized water (30 ml), dried with magnesium sulfate, and then concentrated under a reduced pressure. The residue was added with 66 ml of ethyl acetate and then heated up to at 60° C. 40 ml of n-Heptane was added dropwise at a temperature of 60 to 65° C. for 40 minutes. After finishing the dropwise addition, the solution was gradually cooled down to a room temperature (about 20 to about 25° C.), followed by filtration to collect bicalutamide (12.24 g, yield 91.2%) as crystals. Purity 99.97%.

1. customproduced by a method
2. additionwere sequentially added
3. stirringagitated for 1 hour
4. customsubjected to a phase separation
5. extractionThe water layer was extracted with ethyl acetate (30 ml)
6. washthe combined organic layer was washed with an aqueous solution
7. dissolutiondissolving 3.0 g of sodium pyrosulfite in de-ionized water (30 ml)
8. dry with materialdried with magnesium sulfate
9. concentrationconcentrated under a reduced pressure
10. additionThe residue was added with 66 ml of ethyl acetate
11. temperatureheated up to at 60° C
12. addition40 ml of n-Heptane was added dropwise at a temperature of 60 to 65° C. for 40 minutes
13. additionthe dropwise addition
14. temperaturethe solution was gradually cooled down to a room temperature (about 20 to about 25° C.)
15. filtrationfollowed by filtration