Synthesis
The general procedure for the synthesis of 2,4-dibromo-5-nitropyridine from 4-methoxy-5-nitropyridin-2(1H)-one is as follows: step 2. Phosphoribromide (5.73 g, 20 mmol) was slowly added to a suspension of the product of step 1 (1.70 g, 10 mmol) in acetonitrile (20 mL) at room temperature. Subsequently, the reaction mixture was heated to reflux and maintained for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature and carefully poured into ice water and left to stratify. The aqueous layer was extracted with ethyl acetate (EtOAc) and the organic phases were combined. The organic phase was washed sequentially with water and saturated brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to give the title compound 2,4-dibromo-5-nitropyridine (2.1 g, 75% yield) as a dark solid.
References
[1] Patent: WO2005/37197, 2005, A2. Location in patent: Page/Page column 94
[2] Patent: WO2005/37197, 2005, A2. Location in patent: Page/Page column 94
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 5, p. 1508 - 1511
[4] Patent: WO2006/113837, 2006, A2. Location in patent: Page/Page column 36; 63
[5] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 1, p. 42 - 46
