5-Bromo-2-chlorobenzoyl chloride → (5-Bromo-2-chloro-phenyl)-[4-(2,2-difluoroethoxy)phenyl]methanone

Temperature

0 °C

Under Ar protection, 5-bromo-2-chloro-benzoyl chloride 12n (37.7 g, 148.6 mmol) was dissolved in 350 mL dichloromethane and 2,2-difluoroethoxybenzene 12c (25 g, 158.6 mmol) was added and stirred until dissolved, and cooled to 0° C., followed by addition of AlCl3 (19.1 g, 142.4 mmol) in batch. The reaction mixture was stirred for 2 hours at 0° C., then poured into 300 mL ice water and stirred for 30 minutes and partitioned. The aqueous layer was extracted with dichloromethane (100 mL). The organic layer was combined and partitioned after methanol (50 mL), dichloromethane (100 mL) and water (200 mL) were added. The organic layer was washed with saturated NaCl solution (200 mL) and combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (5-bromo-2-chloro-phenyl)-[4-(2,2-difluoroethoxy)phenyl]methanone 12o (56 g, yellow grease), yield: 99.0%.

1. dissolutionuntil dissolved
2. stirringThe reaction mixture was stirred for 2 hours at 0° C.
3. stirringstirred for 30 minutes
4. custompartitioned
5. extractionThe aqueous layer was extracted with dichloromethane (100 mL)
6. custompartitioned after methanol (50 mL), dichloromethane (100 mL) and water (200 mL)
7. additionwere added
8. washThe organic layer was washed with saturated NaCl solution (200 mL)
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationThe filtrate was concentrated under reduced pressure

ORD record

ord-a5f591c02ee4406989d380e44191180b

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609622B2