2-Bromo-2-methylpropionyl bromide → HCID 67332528, compound

Methyl 5-amino-4-hydroxy-2-(trifluoromethyl)benzoate (53.0 g) was dissolved in chloroform (200 ml) and tetrahydrofuran (200 ml), and thereto was added an aqueous sodium hydrogen carbonate solution (27.60 g/240 ml), and the mixture was vigorously stirred. The mixture was cooled in an ice-bath, and thereto was slowly added dropwise 2-bromoisobutyryl bromide (65.5 g), and the mixture was stirred for 30 minutes. The mixture was warmed to room temperature, and further stirred for 2.5 hours. After the reaction was complete, the mixture was extracted twice with chloroform (300 ml). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to give methyl 5-[(2-bromo-2-methylpropanoyl)amino]-4-hydroxy-2-(trifluoromethyl)benzoate. This crude product was diluted in N,N-dimethylformamide (500 ml), and thereto was added potassium carbonate (60.53 g), and the mixture was stirred at 50° C. for 5 hours. After the reaction was complete, the mixture was cooled to room temperature, and the obtained solid was removed by filtration. To the filtrate was added ethyl acetate (500 ml), and the mixture was washed with a 1N hydrochloric acid (500 ml) and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product, which was crystallized from ethyl acetate/hexane (5/1, 200 ml) to give the title compound (48.5 g).

1. temperatureThe mixture was cooled in an ice-bath
2. stirringthe mixture was stirred for 30 minutes
3. stirringfurther stirred for 2.5 hours
4. extractionthe mixture was extracted twice with chloroform (300 ml)
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure

ORD record

ord-f9fd1f9c82a54f1685cf57933d41ef89

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08389511B2