Dimethylformamide → 2-(3-Bromo-5-chlorophenoxy)-3-chloro-6-fluorobenzaldehyde

To a solution of 3-bromo-5-chlorophenyl 2-chloro-5-fluorophenyl ether (100 g, 298 mmol) in THF (300 mL) cooled to −78° C. over a dry ice/acetone bath was added 1.8M lithium diisopropylamide in hexanes/THF/ethylbenzene (174 mL, 313 mmol) over 10 min. The resulting mixture was stirred for 20 minutes and then treated with DMF (46.1 mL, 595 mmol). The DMF-treated mixture was then removed from the cooling bath and allowed to warm to room temperature and then left at room temperature for 1 hour. The reaction mixture was then quenched with water (1000 mL) and extracted with EtOAc (3×500 mL). The combined extracts were washed with water (500 mL), dried over MgSO4, and concentrated in vacuo. This residue was purified on a silica gel column (0-40% CH2Cl2/hexanes) to give the title product. LRMS (M−18+1)=346.7

1. customwas then removed from the cooling bath
2. waitleft at room temperature for 1 hour
3. customThe reaction mixture was then quenched with water (1000 mL)
4. extractionextracted with EtOAc (3×500 mL)
5. washThe combined extracts were washed with water (500 mL)
6. dry with materialdried over MgSO4
7. concentrationconcentrated in vacuo
8. customThis residue was purified on a silica gel column (0-40% CH2Cl2/hexanes)

ORD record

ord-8885cff276954a648eba22cc64f24ba9

Source dataset

uspto-grants-2010_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07781454B2