Synthetic Route of 187242-88-2, Researchers who often do experiments know that organic synthesis is a process of preparing more complex target molecules from simple raw materials through one or more chemical reactions. Generally, it requires fewer steps,and cheap raw materials. 187242-88-2, name is 2-Chloro-3-nitro-6-phenylpyridine. A new synthetic method of this compound is introduced below.
1? (48.0 g, 1.0 equiv.), 2? (59.0 g, 1.1 equiv.), and Na2CO3 (43.4 g, 2.0 equiv.) were charged to a 2 L, 3-neck flask. DMA (310 mL, 6.5 vol.) was added and the reaction was heated to 100 C. After 18.5 hours, HPLC analysis showed the reaction to be complete. The reaction was cooled to 9 C. and 2-MeTHF (960 mL, 20 vol.) was added. 10% aqueous solution of NaCl (720 mL, 15 vol.) was added resulting in some solid formation. The mixture was stirred for one hour and then transferred to a separatory funnel (rinsed the solids forward with 100 mL water). The layers were separated and the aqueous layer (Vaq1200 mL) was back extracted with 2-MeTHF (2×200 mL). The combined organics were then washed with 10% aqueous solution of NaCl (2×250 mL) and then analyzed by 1H NMR for DMA (0.3 wt %). After holding the solution overnight, an aliquot was taken out (6 mL) and was washed (3 mL) with water which resulted in a nice phase split (took >30 minutes). Water (650 mL, batch size) was added and stirred for 10 minutes and then transferred to a separatory funnel and allowed to sit. After 90 minutes, a partial phase split was realized (Vaq=250 mL). Brine (250 mL) was added resulting in a phase split. The organic layer (1300 mL, 27 vol., Kf=3.45%) was split off and charged to a 3-L RB flask. The flask was heated (atmospheric) to distill off some of the 2-MeTHF. Once 15 volumes of 2-MeTHF (720 mL) remained (30 minutes), the solution was reanalyzed for water content (Kf=0.24%). The reaction was then cooled to 50-55 C. and polished filtered through filter paper (very little solids present). The solution was then recharged to the 3-L flask (after cleaning flask) and the solution was distilled down to 9 volumes (430 mL). The solution was then heated to 70 C. and heptane was added in portions over one hour. The heat was then turned off and the solution was allowed to slowly cool to room temperature (after one hour the temperature was 48 C.). After stirring for 70 hours, the mother liquor was checked by HPLC analysis for 3 (2.7 mg/mL) and then filtered. The solids were washed with a 25% 2-MeTHF/heptane solution (75 mL, slurry) followed by 2×240 mL displacement wash with the same solution. The cake was washed one more time with heptane (240 mL) and then dried in a vacuum oven for 20 hours at room temperature. 3 (81.1 g, 86% yield, 99.2% AUC) was isolated as a dark red solid. 1H NMR (CDCl3) analysis showed no residual solvent present.
At the same time, in my other blogs, there are other synthetic methods of this type of compound,187242-88-2, 2-Chloro-3-nitro-6-phenylpyridine, and friends who are interested can also refer to it.
Reference:
Patent; ArQule, Inc.; Bates, Craig; Chen, Jian-Xie; Mao, Jianmin; Reed, David P.; US2015/266876; (2015); A1;,
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