Synthesis
Under argon protection, phosphorus bromide oxide (4 g, 14.2 mmol) was heated to 90 °C until the solid was completely dissolved. To this hot solution was added 2,8-bis(trifluoromethyl)-4-hydroxyquinoline (4.08 g, 14.2 mmol) and the temperature of the oil bath was raised to 150 °C. After 6 hours of reaction, the mixture was cooled to room temperature. The reaction was quenched by the addition of ice water and the resulting precipitate was filtered and washed with cold water to afford the target product 4-bromo-2,8-bis(trifluoromethyl)quinoline (4.70 g, 96% yield) as a white solid. Thin layer chromatography (TLC) Rf value was 0.79 (unfolding agent: cyclohexane/ether=5:1). Melting point: 60°C. 1H NMR (300 MHz, CDCl3) δ 7.82 (t, J=7.9 Hz, 1H), 8.11 (s, 1H), 8.22 (d, J=7.3 Hz, 1H), 8.46 (d, J=8.6 Hz, 1H). 13C NMR (125 MHz, CDCl3) δ 120.9 (q, J= 276.0 Hz), 122.0 (q, J=2.0 Hz), 123.6 (q, J=273.8 Hz), 128.9, 129.4, 129.8 (q, J=30.8 Hz), 130.5 (q, J=5.3 Hz), 131.5, 138.5, 144.5, 148.6 (q, J=36.1 Hz). Infrared spectra (IR) νmax: 1577, 1422, 1302, 1136, 1098, 1010, 876, 824 cm-1. gas chromatography-mass spectrometry (GC-MS) m/z: 343. high-resolution mass spectrometry (HRMS) calculated value of C11H4BrF6Na(M+Na)+: 365.9329, measured value: 365.9346.
References
[1] Angewandte Chemie - International Edition, 2015, vol. 54, # 47, p. 14070 - 14074
[2] Angew. Chem., 2015, vol. 127, # 47, p. 14276 - 14280,5
[3] Journal of Organic Chemistry, 2016, vol. 81, # 20, p. 9567 - 9575
[4] Tetrahedron Asymmetry, 2011, vol. 22, # 2, p. 138 - 148
[5] Patent: WO2012/107532, 2012, A1. Location in patent: Page/Page column 20-21
