1-chloro-5-fluoro-2-methyl-4-nitrobenzene

b) Synthesis of the aromatic nitro compounds;: 55 g (380 mmol) 2-chloro-4-fluoro toluene are dissolved in 500 ml cone. sulfuric acid and cooled to-5 to 0 °C in an ice bath. To this solution, 50.6 g (500 mmol) KNO3 is added in portions within 1 h. The reaction mixture is allowed to warmed up to room temperature overnight and then poured onto ice. After customary workup, 60 g (81 percent) 27 (Rt. = 2.73 min (method C) ) is obtained as a yellow oil which crystallises in the refrigerator.55 g (380 mmol) 2-Chloro-4-fluoro toluene are dissolved in 500 ml concentrated sulfuric acid and cooled to-5-0 °C in an ice bath. To this solution, 50.6 g (500 mmol) potassium nitrate are added in several portions within 1 h. The reaction mixture is warmed up to room temperature overnight and then poured onto ice. The yellow suspension is extracted 3x with 11 tert. - Butyl-methylether each time and the combined organic phases are washed neutral with NaHCO3-solution. The organic phase is stirred with Na2SO4 and 10 g charcoal, filtered and the filtrate is evaporated to dryness. Yield : 60 g (81 percent) 6, yellow oil, which crystallises in the refrigerator55 g (380 mmol) 2-Chloro-4-fluoro toluene in 500 ml conc. Sulfuric acid are cooled to-5-0 °C gekuehlt and treated within one hour with 50.6 g (500 mmol) potassium nitrate in several portions. The reaction mixture is allowed to warm up to room temperature overnight and then poured onto ice. The yellow suspension is extracted 3x with 11 tert.-Butyl-methylether and the combined organic phases are washed neutral using NaHCO3-solution. The organic phase is stirred with Na2SO4 and 10 g charcoal, filtered and and the filtrate is evaporated. Yield : 60 g (81 percent) 25, yellow oil, crystallises in the refrigerator 0.55 g (2.81 mmol) 25 in DMF are treated with 0.59 g (3.38 mmol) N-Boc-N- methylaminoethanol and 2.11 g (6.47 mmol) cesium carbonate and stirred overnight at 50 °C. the reaction mixture is filtered and the filtrate is evaporated. The residue is taken up in ethylacetate, washed with water, dried using Na2SO4, filtered and evaporated. Yield : 0.94 g (97 percent), brown oil The thus obtained nitro compound is hydrogenated in THF at room temperature using H2 and Raney-Ni. The catalyst is removed by filtration and the filtrate is evaporated to dryness. Yield : 0.83 g (96 percent) 26, brown oil2-Chloro-4-fluoro-1-methylbenzene (5.000 g, 34.585 mmol) and Potassium nitrate (4.371 g, 43.232 mmol) was added to a mixture of sulfuric acid (12.536 mL, 235.180 mmol) at 0 & The mixture was slowly added so that the internal temperature did not exceed 10 ° C, slowly raised to room temperature, and stirred for 22 hours.The reaction mixture was cooled in an ice bath and poured into 50 ml of water. After completion of the reaction, the mixture was extracted three times with 50 ml of ethyl acetate.The combined organic layers were washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure.The concentrate was purified by column chromatography (SiO2, 80 g cartridge; ethyl acetate / hexane = 0percent to 5percent) and concentrated to give 1-chloro-5-fluoro-2-methyl- , 51.2percent) as a pale yellow liquid.2-Chloro-4-fluoro-5-nitrotoluene. Step 1: 1-Chloro-5-fluoro-2-methyl-4-nitrobenzene