31568-91-9

General procedure for the synthesis of 2-chloro-8-hydroxyquinoline from 2,8-quinolinediol: Thionyl chloride (3.56 ml, 49.6 mmol) was added slowly and dropwise to a suspension of N,N-dimethylformamide (20 ml) in 2,8-quinolinediol (2.00 g, 12.4 mmol) under ice-bath cooling and stirring conditions. The reaction mixture was stirred at room temperature for 2 h. After that, thionyl chloride (3.56 ml, 49.6 mmol) was added again and the reaction temperature was raised to 50 °C and stirring was continued for 3.5 h. The reaction mixture was then stirred for 3.5 h. The reaction temperature was raised to 50 °C and stirring was continued. After completion of the reaction, the reaction solution was cooled to room temperature, poured into ice water and extracted with ethyl acetate. The organic phase was washed with water, dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/20) to afford 2-chloro-8-hydroxyquinoline (1.72 g, 77% yield) as a pale yellow solid. The product had a melting point of 79-80 °C, APCI-MS m/z 180/182 [M+H]+.

[1] Patent: EP2634177, 2013, A1. Location in patent: Paragraph 0217; 0218
[2] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 790 - 799
[3] Canadian Journal of Chemistry, 2005, vol. 83, # 5, p. 460 - 470
[4] Patent: WO2004/35549, 2004, A1. Location in patent: Page 71
[5] Patent: WO2014/100730, 2014, A1. Location in patent: Paragraph 00314