Nitric Acid → 2-Bromo-4-methoxy-1-nitrobenzene

Temperature

50 °C

Nitric acid (70%, 5 mL) was placed in a 25 mL round-bottomed flask. Concentrated sulphuric acid (4 mL) was then added dropwise with stirring. The mixture was kept cool during the addition by immersing the flask in an ice bath. 3-Methoxybromobenzene (4 g, 21.5 mmol) was then introduced dropwise. The reaction mixture was then heated to 50° C. and stirred for 5 h. After cooling, the mixture was poured into 100 mL of cold water and extracted with ethyl acetate (30 mL×3). The organic layers were combined and washed with water (50 mL×4) and brine. The ethyl acetate layer was dried with anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using 95:5 hexanes:ethyl acetate. The first compound that eluted from the column was 3-methoxy-4-nitrobromobenzene (1.2 g) in 24% yield; 1H NMR (CDCl3) δ3.96(3H, s), 7.17 (1H, dd, J1=8.6, J2=1.9), 7.24 (1H, d, J=1.9), 7.75 (1H, d, J=8.6); 13C NMR δ57.34 117.58, 124.00, 127.41, 129.05, 142.26, 154.02. The second compound eluting from the column was 24 (1.5 g, 30% yield); 43-45° C.; 1H NMR (CDCl3) δ3.89 (3H, s), 6.91 (1H, dd, J1=9.1, J2=2.7), 7.21 (1H, d, J=2.7), 7.98 (1H, d, J=9.1); 13C NMR δ56.68, 114.02, 117.29, 120.61, 128.46, 163.23.

1. temperatureThe mixture was kept cool during the addition
2. stirringstirred for 5 h
3. temperatureAfter cooling
4. extractionextracted with ethyl acetate (30 mL×3)
5. washwashed with water (50 mL×4) and brine
6. dry with materialThe ethyl acetate layer was dried with anhydrous sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe crude product was purified by column chromatography on silica gel using 95:5 hexanes
9. washThe first compound that eluted from the column
10. washThe second compound eluting from the column

ORD record

ord-4e8e99382e4040fa86a0d6df93897fda

Source dataset

uspto-grants-2004_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06740650B2