Synthesis
General procedure for the synthesis of 4-chloro-3-nitroquinoline from 4-hydroxy-3-nitroquinoline: The intermediate 3-nitro-4-hydroxyquinoline (18.7 g, 98.4 mmol) was suspended in dichloromethane (150 mL). Thionyl chloride (17.2 mL, 236 mmol) and N,N-dimethylformamide (DMF, 9.2 mL, 118 mmol) were added sequentially to the suspension. The reaction mixture was heated to reflux and kept reacting overnight. Upon completion of the reaction, the mixture was slowly poured into ice water. The organic and aqueous layers were separated and the organic layer was washed sequentially with saturated sodium bicarbonate solution, water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue (20.52 g, 93% yield) can be used directly in the subsequent reaction without further purification.
References
[1] Patent: EP2674170, 2013, A1. Location in patent: Paragraph 0228
[2] Patent: US2014/141033, 2014, A1. Location in patent: Page/Page column
[3] Journal of Medicinal Chemistry, 1991, vol. 34, # 3, p. 1202 - 1206
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 11, p. 3354 - 3361
[5] Patent: WO2007/89507, 2007, A1. Location in patent: Page/Page column 20-21
