1-Chloro-5-isopropoxy-2-methyl-4-nitrobenzene

2-Chloro-4-fluoro-5-nitrobenzene (25 g, 131 mmol) was dissolved in isopropanol (250 mL) and cesium carbonate(208 g, 659 mmol) was added thereto. The reaction mixture was stirred at 60 °C for 16 hours. The reaction mixture was cooled to room temperature and the reaction mixture was concentrated under reduced pressure. The residue wasdissolved in ethyl acetate (250 mL) and then water (250 mL) was added. The separated organic phase was dried overanhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purifiedby silica gel column chromatography (petroleum ether: ethyl acetate = 19: 1) to deliver a yellow solid 13-d (28.7 g, yield:95percent).1H-NMR (400MHz, DMSO-d6) δ: 7.90 (d, J=0.6Hz, 1H), 7.52 (s, 2H), 7. 86 (m, 1H), 2.30 (s, 3H), 1.27 (d, J=6Hz, 6H) ppm.1.5 L of isopropanol, 1-chloro-5-fluoro-2-methyl-4-nitrobenzene (260 g)Potassium hydroxide (116g) was added to complete the reaction at a temperature of 20 ° C to monitor the disappearance of the raw materials. The stirring was stopped and the reaction solution was added to 5L of water overThe product was filtered and the filter cake was dried to give 1-chloro-5-isopropyloxy-2-methyl-4-nitrobenzene, 271 g, yield: 86.3percent.The title compound 2-chloro-4-fluoro-5-nitrotoluene (i.e., compound 2-1, 14.2 g, 74.9 mmol) was dissolved in isopropanol (100.0 mL)Cesium carbonate (122.0 g, 374.4 mmol) was added, The reaction was carried out at 60 ° C overnight.After completion of the reaction, the mixture was concentrated to remove isopropanol, Poured into 500.0mL water, extracted with ethyl acetate, the organic phase was dried with anhydrous sodium sulfate, concentrated, Compound No. 2-2 (14.4 g) was obtained in a yield of 82.0percent.The title compound 2-chloro-4-fluoro-5-nitrotoluene (i.e., Compound 2-1, 14.2 g, 74.9 mmol) was dissolved in isopropanol (100.0 mL), cesium carbonate (122.0 g, 374.4 mmol) The reaction mixture was concentrated at 60 ° C overnight. After completion of the reaction, the mixture was concentrated to remove isopropanol, poured into 500.0 mL of water, extracted with ethyl acetate. The organic phase was dried over anhydrous sodium sulfate and concentrated to give Compound 2-2 (14.3 g), yield: 82.0percent.1-Chloro-5-fluoro-2-methyl-4-nitrobenzene (3.260 g, 17.197 mmol)Cesium carbonate (28.015 g, 85.984 mmol) was added to a solution ofPropanol (35 mL) at 60 ° C was stirred at the same temperature for 24 hours, and then the temperature was lowered to room temperature to terminate the reaction. The reaction mixture was filtered through a paper filter to remove the solid. The solvent was removed from the filtrate under reduced pressure, water was poured into the resulting concentrate, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, The water was removed with magnesium sulfate, filtered and concentrated under reduced pressure.The concentrate was purified by column chromatography (SiO2, 40 g cartridge; ethyl acetate / hexane = 5percent) and concentrated to obtain 2.938 g (74.4percent) of 1-chloro-5-isopropoxy-2-methyl-4-nitrobenzene As a light brown solid.

Molecular Weight:229.66
XLogP3:3.5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:229.0505709
Monoisotopic Mass:229.0505709
Topological Polar Surface Area:55
Heavy Atom Count:15
Complexity:229
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes