3-BROMO-4-CHLORO-5-NITROPYRIDINE

Application

3-Bromo-4-chloro-5-nitropyridine can be used as an organic synthesis intermediate and a pharmaceutical intermediate in laboratory research and development processes and in the synthesis of pharmaceutical chemicals.

Synthesis

Step 2. Synthesis of 3-bromo-4-chloro-5-nitropyridine The product of Step 1, 3-bromo-4-hydroxy-5-nitropyridine (6.57 g, 30 mmol), was slowly added to phosphoryl chloride (50 mL) under ice bath cooling conditions. Subsequently, N,N-diethylaniline (4.77 mL, 30 mmol) was added dropwise to the stirring reaction mixture. The reaction mixture was gradually warmed to room temperature and then heated to reflux for 2 hours. After completion of the reaction, the mixture was concentrated under reduced pressure and the residue was carefully poured into ice water. The aqueous phase was extracted with ether and the organic phases were combined and washed sequentially twice with water and once with brine. Finally, the organic phase was concentrated to give a brown oil, which solidified to the target product 3-bromo-4-chloro-5-nitropyridine in a yield of 8.01 g (yield >100%) after standing.

References

[1] Patent: WO2005/37198, 2005, A2. Location in patent: Page/Page column 26-27
[2] Patent: WO2005/37198, 2005, A2. Location in patent: Page/Page column 26-27
[3] Tetrahedron Letters, 2012, vol. 53, # 4, p. 377 - 379
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2462 - 2471
[5] Justus Liebigs Annalen der Chemie, 1937, vol. 529, p. 291