Benzene, 1-fluoro-5-methoxy-2-methyl-4-nitro- (9CI)

106579-00-4

314298-13-0

The general procedure for the synthesis of 1-fluoro-5-methoxy-2-methyl-4-nitrobenzene from 5-methoxy-2-methyl-4-nitroaniline is as follows: pyridine (47.4 mL, 0.48 mol) and 70% hydrogen fluoride are placed in a plastic dispensing funnel under nitrogen protection and added dropwise to a plastic reaction flask at -78°C (dry ice/acetone bath) over a period of 20 minutes. Note: This process is an exothermic reaction. After the dropwise addition was completed, stirring of the reaction mixture was continued for 10 minutes. Subsequently, 5-methoxy-2-methyl-4-nitroaniline (9.11 g, 0.05 mol) was added and stirring was continued for 10 minutes. Next, sodium nitrite (5.8 g, 0.08 mol) was added and stirring was continued for 10 minutes at -78 °C. The reaction mixture was gradually warmed up to room temperature and then heated to 60 °C and maintained at this temperature for 2 hours. Upon completion of the reaction, it was cooled to room temperature and the reaction was quenched by the addition of an ice/water mixture (300 mL). The precipitate was collected by vacuum filtration, washed with water and dried under vacuum. The resulting solid product was recrystallized with methylcyclohexane to give the yellow crystalline title product 1-fluoro-5-methoxy-2-methyl-4-nitrobenzene (5.8 g, 63% yield). The structure of the product was confirmed by 1H NMR (300 MHz, chloroform-d): δ 7.82 (d, 1H), 6.75 (d, 1H), 3.93 (s, 3H), 2.25 (d, 3H).