Chlorodifluoromethane → 1-Bromo-3-(difluoromethoxy)-5-fluorobenzene

Temperature

82.5 °C

A mixture of 3-bromo-5-fluorophenol (6.1 g, 31.0 mmol; see step (ii) above) and chlorodifluoromethane (13.0 g, 150.0 mmol) in i-PrOH (100 mL) and 30% KOH (80 mL) was heated in a sealed flask for 18 h at 80-85° C. The reaction mixture was cooled to room temperature and the layers were separated. The organic layer was concentrated in vacuo to afford a colourless oil. The aqueous layer was extracted with Et2O (3× 30 mL). The crude oil and the combined organic extracts were washed with 2N NaOH (3× 30 mL) and H2O (3× 30 mL). The organics were then dried (Na2SO4), filtered through a small silica gel plug, and concentrated in vacuo to afford the sub-title compound (6.1 g, 79%) as a colourless oil that was used without further purification.

1. temperatureThe reaction mixture was cooled to room temperature
2. customthe layers were separated
3. concentrationThe organic layer was concentrated in vacuo
4. customto afford a colourless oil
5. extractionThe aqueous layer was extracted with Et2O (3× 30 mL)
6. washThe crude oil and the combined organic extracts were washed with 2N NaOH (3× 30 mL) and H2O (3× 30 mL)
7. dry with materialThe organics were then dried (Na2SO4)
8. filtrationfiltered through a small silica gel plug
9. concentrationconcentrated in vacuo

ORD record

ord-9d9385364060452f83215b17ba395d9c

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645751B2