Dimethylformamide → 4-Bromo-2-methoxy-1-(trifluoromethyl)benzene

Temperature

0 °C

To a 250 mL round-bottomed flask was added 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (12 mL, 50 mmol) and DMF (4.0 mL, 50 mmol). The solution was stirred at 0° C. and treated with sodium methoxide (4 g, 75 mmol). The reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours. The resulting milky suspension was quenched with ice at 0° C. and the separated aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated sodium chloride (1×25 mL), dried over Na2SO4, and concentrated to give the crude residue which was purified with flash column chromatography ((5%→20% EtOAc in hexane) to provide 4-bromo-2-methoxy-1-(trifluoromethyl)benzene (5.80 g, 46% yield) as a light yellow oil. m/z (%): 256.1.2 (100%, M++H).

1. stirringThe reaction mixture was stirred at room temperature for 30 minutes and 60° C. for 2 hours
2. customThe resulting milky suspension was quenched with ice at 0° C.
3. extractionthe separated aqueous layer was extracted with EtOAc (3×50 mL)
4. washThe combined organic layers were washed with saturated sodium chloride (1×25 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated
7. customto give the crude residue which
8. customwas purified with flash column chromatography ((5%→20% EtOAc in hexane)

ORD record

ord-2b7e295d88e849f2a5d98d3f6a2e4997

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084479B2