2,6-Dichloro-4-methyl-3-nitropyridine

Step 109.1: 2, 6-dichloro-4-methyl-3-nitropyridine To a suspension of 759 2, 6-dichloro-4-methylpyridine (1 g, 6.17 mmol) in trifluoroacetic acid anhydride (5 mL, 35.4 mmol) cooled down to 0° C. was added dropwise nitric acid (0.579 mL, 12.96 mmol) into it. The resulting solution was stirred at RT for 18 hr. The reaction mixture was added slowly to a chilled solution of sodium metabisulfite (1.183 g, 6.17 mmol) in water (8 mL) and stirred at RT for 2 hr. The reaction mixture was neutralized to pH 7 using 8N NaOH solution and extracted twice with CHTo a suspension of 2, 6-dichloro-4-methylpyridine (1 g, 6.17 mmol) in trifluoroacetic acid anhydride (5 mL, 35.4 mmol) cooled down to 0 00 was added dropwise nitric acid (0.579 mL, 12.96 mmol) into it. The resulting solution was stirred at RT for 18 hr. The reaction mixture wasadded slowly to a chilled solution of sodium metabisulfite (1.183 g, 6.17 mmol) in water (8 mL) and stirred at RT for 2 hr. The reaction mixture was neutralized to pH 7 using 8N NaOH solution and extracted twice with CH2CI2. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the title product (1.187 g, 5.73 mmol, 93percent yield) as white solid. tR: 1.07 mm (LC-MS 2); ESI-MS: 208 [M+H] (LC-MS2); 1H NMR (400 MHz, DMSO-d6) O ppm 2.39 (5, 3 H) 7.90 (5, 1 H).Nitric acid (1.5 mL, 33.6 mmol) was added to a solution of sulfuric acid (2.5 mL, 46.9 mmol) stirred under nitrogen at 0° C. Then 2, 6-dichloro-4-methylpyridine (0.500 g, 3.09 mmol) was added at 0° C. Then the reaction mixture was stirred at 100° C. for 16 hr. The reaction was monitored by TLC. After completion, the reaction mixture was quenched with crushed ice and neutralized with NHNitric acid (1.5 mL, 33.6 mmol) was added to a solution of sulfuric acid (2.5 mL, 46.9 mmol) stirred under nitrogen at 0°C. Then 2, 6-dichloro-4-methylpyridine (0.500 g, 3.09 mmol) was added at 0°C. Then the reaction mixture was stirred at 100 °C for 16 hr. The reaction was monitored by TLC. After completion, the reaction mixture was quenched with crushed ice and neutralized with NH4OH solution and filtered the solid and dried under vacuum to give the desired product (0.300 g, 1.443 mmol, 46.8 percent yield) as a pale yellow solid, LCMS (m/z) 206.8 [M+H]+.2, 6-Dichloro-4-methylpyridine (238 g, 1469 mmol) was dissolved in TFA (1.9 L) and fuming nitricacid (197 mL, 4407 mmol).TFAA was added while maintaining the temperature below 30°Cusing an ice/water bath. The reaction mixture was stirred for 4 h at rt and poured into ice water (8 L). The resulting suspension was filtered. The filter cake was washed with water (2 L) and dried in vacuo at 3000 to afford the title compound (256 g) as colorless crystals. Rt: 1.06 mm (LC-MS 1); MS mlz: 207.0 [M](LC-MS 1).b) 2, 6-Dichloro-4-methyl-3-nitropyridine (A99) 2-Chloro-4-methyl-5-nitropyridine-1 -oxide A98 (2.528 g, 13.4 mmol) was stirred in POCIFuming nitric acid (20 mL) was added drop-wise to an ice-cooled solution of 2 , 6-dichloro-4-methylpyridine (18.5 mmol, 3.0 g) in concentrated sulfuric acid (20 mL) . The resulting solution was heated at 90 C for 18 hours. (1267) The solution was cooled to room temperature and poured into a mixture of ice and water. After allowing to warm to room temperature, the suspension was filtered and the filter cake was washed with water. After drying in air, the title compound was obtained as a pale yellow solid (1268) (1.32 g, 36%; 3:1 mixture with 3 , 5-dinitro-2 , 6-dichloro- 4-methylpyridine) .

Molecular Weight:207.01
XLogP3:3
Hydrogen Bond Acceptor Count:3
Exact Mass:205.9649828
Monoisotopic Mass:205.9649828
Topological Polar Surface Area:58.7
Heavy Atom Count:12
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes