With the rapid development and complex challenges of chemical substances, the synthesis of new drugs is usually one of the most effective ways to increase yield.22280-56-4, name is 2-Chloro-3-methyl-5-nitropyridine, molecular formula is C6H5ClN2O2, molecular weight is 172.5691, as common compound, the synthetic route is as follows.SDS of cas: 22280-56-4
3-Methyl-5-nitropyridin-2-ol (134 g, 0.872 mol) (J. Org. Chem. 1949, 14, 328-332) was divided into 3 portions and placed in three 1-L round bottom flasks. POCl3 (200 mL) was added to each flask and the mixtures were heated to reflux for 2 h. The solutions were cooled and the excess POCl3 was removed in vacuo. The residues were poured into ice water (1 L) with stirring and the precipitates were collected by filtration and air dried for 20 min. The combined products were recrystallized from 10% ethyl acetate in hexanes (300 mL) and air dried to give 2-chloro-3-methyl-5-nitropyridine (139 g, 92% yield) as a white solid which was used in the next step without further purification: 1H NMR (300 MHz, CDCl3) delta 9.04 (d, J=2.5 Hz, 1H), 8.33 (d, J=2.2 Hz, 1H), 2.50 (s, 3H).2-Chloro-3-methyl-5-nitropyridine (139 g, 0.806 mol) from the above procedure was divided into two portions and placed in two 2-L round bottom flasks with methanol (500 mL). The solutions were cooled in dry ice/isopropanol baths as solid sodium methoxide (26.5 g, 0.467 mol) was added portion-wise to each flask so that the temperature was remained below 20 C. When the additions were complete, the resulting mixtures were heated to reflux for 1 h. The mixtures were cooled and diluted with ice water (500 mL) to give white precipitates, which were collected by filtration. The combined filtrates were washed with water and air dried to give 2-methoxy-3-methyl-5-nitropyridine (127 g, 97% yield) as a white solid: 1H NMR (400 MHz, CDCl3) delta 8.91 (d, J=2.0 Hz, 1H), 8.16 (s, 1H), 4.06 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3) delta 165.83, 141.91, 139.37, 132.92, 121.77, 54.83, 15.84. An analytical sample was recrystallized from hexane to give white needles, mp 95-96.5 C. Anal. calcd. for C7H8N2O3: C, 50.00, H, 4.79, N, 16.66. Found: C, 49.73, H, 5.02, N, 16.48.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,22280-56-4, 2-Chloro-3-methyl-5-nitropyridine, and friends who are interested can also refer to it.
Reference:
Patent; Bristol-Myers Squibb Company; US2010/29684; (2010); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem