Uses
2,5-Dichloroquinoline can be used as a pharmaceutical synthesis intermediate.
Synthesis
Step 2: Preparation of 5-chloro-2-chloroquinoline (compound 181-3)
To a solution of 5-chloroquinoline azide (compound 181-2, 19 g, 106 mmol) in dichloromethane (DCM, 250 mL) was added phosphorus oxychloride (POCl3, 32 g, 212 mmol). The reaction mixture was heated to 40°C and stirred for 1.5 hours. Upon completion of the reaction, saturated aqueous sodium bicarbonate (NaHCO3) solution (500 mL) was slowly added and the mixture was stirred at 15°C for 10 minutes. Subsequently, the aqueous phase was extracted with ethyl acetate (300 mL x 3). The organic phases were combined, washed with brine (500 mL), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuum. The residue was purified by column chromatography (silica gel 100-200 mesh, column height: 250 mm, diameter: 100 mm, eluent: petroleum ether/ethyl acetate=50/1~20/1) to afford 5-chloro-2-chloroquinoline (Compound 181-3, 9.8 g, 40% yield) as a white solid.
References
[1] Patent: WO2016/54491, 2016, A1. Location in patent: Paragraph 00625
[2] Bioorganic and medicinal chemistry, 2002, vol. 10, # 8, p. 2611 - 2623
[3] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 5, p. 1472 - 1476
