Synthesis
General procedure for the synthesis of 4-chloro-2,8-bis(trifluoromethyl)quinoline from 2,8-bis(trifluoromethyl)-4-hydroxyquinoline: 2,8-bis(trifluoromethyl)quinolin-4-ol (0.25 g, 0.89 mmol) was dissolved in phosphorus trichloride (5 mL) and the reaction was carried out at reflux for 5 h at 80 °C under nitrogen protection. Upon completion of the reaction, the reaction mixture was quenched with 30 mL of ice water and extracted with dichloromethane (2 x 20 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give a light yellow solid product (0.13 g, 50% yield), which could be used in subsequent reactions without further purification.
References
[1] Tetrahedron, 1991, vol. 47, # 36, p. 7609 - 7614
[2] European Journal of Medicinal Chemistry, 2010, vol. 45, # 8, p. 3374 - 3383
[3] Monatshefte fur Chemie, 2008, vol. 139, # 2, p. 179 - 181
[4] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 23, p. 5466 - 5469
[5] Patent: US4429130, 1984, A
