Bromine → N-{3-[(2-amino-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

Temperature

50 °C

To a solution of potassium thiocyanate (18.6 g, 192 mmol) in acetic acid (1.0 L) was added N-[3-(4-amino-2-nitrophenoxy)phenyl]-3-(1-cyano-1-methylethyl)benzamide (20 g, 48 mmol), and the mixture was stirred at 50° C. for 10 min. The obtained solution was cooled to room temperature, a solution of bromine (8.05 g, 50.4 mmol) in acetic acid (200 mL) was slowly added dropwise, and the mixture was stirred at room temperature for 16 hr. Then, a solution of potassium thiocyanate (9.3 g, 96 mmol) and bromine (4.02 g, 25.2 mmol) in acetic acid (100 mL) was added, and the mixture was further stirred at room temperature for 4 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 (600 mL), water (300 mL) was added, and the mixture was neutralized with 8N aqueous sodium hydroxide solution. The organic layer was washed successively with 5% aqueous sodium hydrogen carbonate solution (300 mL) and saturated brine (300 mL×2) and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate). The obtained solution was concentrated under reduced pressure to give the title compound (7.8 g, 34%) as a yellow powder.

1. temperatureThe obtained solution was cooled to room temperature
2. stirringthe mixture was stirred at room temperature for 16 hr
3. stirringthe mixture was further stirred at room temperature for 4 hr
4. filtrationThe resulting yellow insoluble material was filtered off
5. washwashed with acetic acid
6. concentrationthe mixture was concentrated under reduced pressure
7. additionwater (300 mL) was added
8. washThe organic layer was washed successively with 5% aqueous sodium hydrogen carbonate solution (300 mL) and saturated brine (300 mL×2)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationInsoluble material was filtered off
11. customthe filtrate was purified by basic silica gel column chromatography (eluate: ethyl acetate)
12. concentrationThe obtained solution was concentrated under reduced pressure

ORD record

ord-518aefddee9544268e6f77da41508d22

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08143258B2