Toluene → 2-Fluoro-1-methoxy-3-methyl-4-nitrobenzene

Participants

Reaction Conditions

Reaction Steps

Dimethylzinc (67 ml of a 2M toluene) was slowly added to a mixture of 2-bromo-3-fluoro-4-methoxy-1-nitro-benzene (12.0 g) and palladium-(diphenylphosphinoferrocenyl)-dichloride-methylene dichloride complex (1.65 g) in dioxane (300 ml) at 40° C. The mixture was stirred at 55° C. during 2 hours. After cooling to room temperature, MeOH (80 ml) was slowly added followed by aqueous NH4Cl soln. The resulting mixture was extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The crude oil was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate, 9/1) to provide 2-fluoro-1-methoxy-3-methyl-4-nitro-benzene (10.5 g, 90% purity) as a light yellow solid used as such in Step 3. 1H NMR (CDCl3) δ ppm: 7.89 (1H, dd); 6.86 (1H, dd); 3.96 (3H, s); 2.53 (3H, d).

Provenance & Evidence