1-Bromo-5-fluoro-4-methoxy-2-nitrobenzene

A solution of phenol (9c) (25 g, 106 mmol) in DMF (200 mL) was treated with potassium carbonate (28.9 g, 212 mmol) and methyl iodide (12.8 mL, 212 mmol). The reaction mixture was stirred at 60 degree;C for 5 hours and evaporated in vacuo. The mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate and evaporated in vacuo to afford the product as a yellow solid (25.6 g, 97percent). MS (+ve ion electrospray) m/z 251 (MH+).d) 4-bromo~2-fluoro-5-nitrophenyl methyl ether; A solution of 4-bromo-2-fluoro-5-nitrophenol (25 g, 106 mmol) in DMF (200 mL) was treated with potassium carbonate (28.9 g, 212 mmol) and methyl iodide (12.8 mL, 212 mmol). The reaction mixture was stirred at 60 C for 5 hours and evaporated in vacuo. The mixture was partitioned between water and ethyl acetate. The organic layer was dried over magnesium sulfate and evaporated under vacuum to afford the product (25.6 g, 97percent) as a yellow solid. LC-MS (ES) (M+H)+ m/z = 251.Reference 1-Bromo-5-fluoro-4-methoxy-2-nitrobenzene; 5-Fluoro-4-methoxy-2-nitroaniline obtained in Reference (4.1 g) was dissolved in a mixed solvent of water (20 ml) and 1, 4-dioxane (10 ml), 48percent 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 48percent 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, 91percent). 1H-NMR (300 MHz, CDCl3) 5 (ppm): 3. 96 (3H, s), 7. 4 (1H, d, J=9. 9Hz), 7. 58 (1H, d, J=8. lHz).

Molecular Weight:250.02
XLogP3:2.5
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:248.94368
Monoisotopic Mass:248.94368
Topological Polar Surface Area:55
Heavy Atom Count:13
Complexity:199
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes