反应详情

To a solution of N-[5-(4-amino-2-cyanophenoxy)-4-chloro-2-fluorophenyl]-2,2,2-trifluoroacetamide (1.0 g, 2.68 mmol) in acetic acid (20 mL) was added potassium thiocyanate (1.3 g, 13.4 mmol), and the mixture was stirred at room temperature for 10 min. A solution of bromine (513 mg, 3.21 mmol) in acetic acid (10 mL) was slowly added dropwise to the obtained solution. After the completion of the dropwise addition, the mixture was stirred at room temperature for 12 hr. The resulting yellow insoluble material was filtered off and washed with acetic acid. The filtrate and washings were combined and the mixture was concentrated under reduced pressure. The obtained residue was suspended in ethyl acetate (150 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (150 mL×2) and saturated brine (150 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give the title compound (0.71 g, 60%) as a white powder.

1. additionAfter the completion of the dropwise addition
2. stirringthe mixture was stirred at room temperature for 12 hr
3. filtrationThe resulting yellow insoluble material was filtered off
4. washwashed with acetic acid
5. concentrationthe mixture was concentrated under reduced pressure
6. washwashed successively with 5% aqueous sodium hydrogen carbonate solution (150 mL×2) and saturated brine (150 mL)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationInsoluble material was filtered off
9. concentrationthe filtrate was concentrated under reduced pressure
10. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=30/70→80/20)
11. concentrationthe obtained solution was concentrated under reduced pressure
12. customThe residue was recrystallized from ethyl acetate/n-hexane