Bromine → 2-Bromo-1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone

Temperature

33 °C

A 500-mL flask equipped with a mechanical stirrer, thermometer, addition funnel and scrubber was charged with 1-(4,5-dihydro-5-(2,6-difluorophenyl)-3-isoxazolyl)ethanone (i.e. the product of Step B) (60.0 g, 0.27 mmol) and dichloromethane (130 mL). The reaction mixture was heated at 33° C., and a solution of bromine (39.2 mL, 0.24 mol) in dichloromethane (100 mL) was added dropwise via the addition funnel. After about 5 mL of the bromine solution had been added, the addition was stopped and the reaction mixture was stirred at 33° C. for about 10 minutes, during which time the color of the reaction mixture changed from red to yellow. The reaction mixture was cooled to 5° C., and the remaining bromine solution was added dropwise over 90 minutes. After the addition was complete, the reaction mixture was washed with aqueous sodium bisulfite solution (3.5 g in 100 mL of water), the layers were separated and the organic layer was concentrated under reduced pressure. Hexanes were added to the resulting residue, and the mixture was filtered rinsing with hexanes to provide the title compound as a brown solid (73 g), which was used without further purification.

1. customA 500-mL flask equipped with a mechanical stirrer
2. additionthermometer, addition funnel
3. additionthe addition
4. temperatureThe reaction mixture was cooled to 5° C.
5. additionAfter the addition
6. washthe reaction mixture was washed with aqueous sodium bisulfite solution (3.5 g in 100 mL of water)
7. customthe layers were separated
8. concentrationthe organic layer was concentrated under reduced pressure
9. additionHexanes were added to the resulting residue
10. filtrationthe mixture was filtered
11. washrinsing with hexanes

ORD record

ord-135d53f449c744cfa4d33a0559f073dc

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618137B2