Hydrogen Bromide → 1-Bromo-5-fluoro-4-methoxy-2-nitrobenzene

Temperature

0 °C

5-Fluoro-4-methoxy-2-nitroaniline obtained in Reference Example 14 (4.1 g) was dissolved in a mixed solvent of water (20 ml) and 1,4-dioxane (10 ml), 48% hydrobromic acid (12 ml) was added to the solution under refluxing, and then the mixture was refluxed for 15 minutes. The reaction mixture was cooled to 0° C., sodium nitrite was added dropwise thereto, and the mixture was stirred at 0° C. for 15 minutes. The resulting mixture was added dropwise to a solution of copper (I) bromide (3.6 g) in a mixture of water (20 ml) and 48% hydrobromic acid (12 ml) at 0° C. The mixture was stirred at 60° C. for 15 minutes, cooled to room temperature, and further stirred for 1 hour. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography (developing solvent:ethyl acetate-hexane=1:8) to obtain the title compound as crystals (5 g, 91%).

1. additionwas added to the solution
2. temperatureunder refluxing
3. temperaturethe mixture was refluxed for 15 minutes
4. stirringThe mixture was stirred at 60° C. for 15 minutes
5. temperaturecooled to room temperature
6. stirringfurther stirred for 1 hour
7. extractionThe reaction mixture was extracted with ethyl acetate
8. washthe extract was washed with water
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customThe residue was purified by column chromatography (developing solvent:ethyl acetate-hexane=1:8)

ORD record

ord-b8e11dde9c564564ace91efd9a777d22

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07541478B2