4-bromo-2-methoxy-1-nitrobenzene

To a solution of 4-bromo-2-fluoro-1-nitro-benzene (2.0 g, 9.09 mmol) in methanol (50 ml) was added sodium methanolate (30 percent in methanol) (1.64 g, 9.09 mmol). The reac.not. tion mixture was stirred at room temperature overnight. The reaction mixture was con- centrated and the residue was dissolved in water (30 ml) and extracted twice with ethyl acetate. The combined organic phases were washed with water. The organic phase was separated, dried over magnesium sulfate, filtered, and evaporated to dryness to yield a crystalline solid (2.1 g, 99 percent). MeONa (1.0 mL, 5.0 mmol)Was added to a solution of 4-bromo-2-fluoro-1-nitrobenzene (1.01 g, 4.58 mmol)In MeOH (10mL) solution, The reaction was stirred at 60 ° C in an oil bath for 1 h.The solvent was removed under reduced pressure, The residue was dissolved in CH2Cl2 (30 mL)The insoluble material was removed by filtration, The filtrate was concentrated, To give the object as a yellow solid (1.05 g, 98percent).18.4 g (83.64 mmol) of 2-fluoro-4-bromonitrobenzene (Aldrich) are almost fully dissolved in 300 mL of anhydrous methanol. 19.9 mL (106.22 mmol) of a 30percent solution of sodium methoxide in methanol are added dropwise and the mixture is stirred overnight at room temperature.4-Bromo-2-methoxy-1-nitrobenzene (4e). To asolution of 4-Bromo-2-fluoro-1-nitrobenzene (400 mg, 2.0 mmol) in methanol (5 mL) wasadded sodium methoxide 5.0Min methanol (480 L, 2.4 mmol) and then stirred at roomtemperature for 15 h. The reaction mixture was diluted with ethyl acetate, washed with waterand brine, and dried over anhydrous MgSO4. The crude material was purified by silica gelchromatography (6percent ethyl acetate in hexanes) to give 4e (380 mg, 73percent). 1H NMR (600 MHz, Acetone-d6) δ 7.80 (d, J = 8.6 Hz, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 8.6, 1.9 Hz, 1H), 4.04 (s, 3H); 13C NMR (150 MHz, Acetone-d6) δ 154.1, 139.9, 128.4, 127.3, 124.3, 118.3, 57.6;IR (Neat) (cm-1): 3108, 2990, 2957, 2855, 1611, 1567, 1523, 1441, 1396, 1344, 1304, 1258, 1189, 1005, 872, 858. 1H NMR data correspond with those reported in the literature [12].Step 2 At 0 ° C, sodium metal (1.0 g) was chopped and slowly added to 30 mL.In anhydrous methanol, after 1 h of reaction, 2-fluoro-4-bromo-1-nitrobenzene (10.0 g) was added.After reacting at room temperature overnight, the target product is obtained by post-treatment and separation and purification.(white solid, 9.8 g).To 4-bromo-2-fluoro-1-nitrobenzene (8.0 g, 36.4 mmol) was added 0.5 N sodium methoxide (105 mL, 52.5 mmol). The mixture was stirred at 60° C. for 1 h. The MeOH was rotovaped down. The crude product was dissolved in DCM (100 mL), washed with H