[Synthesis]
2-Bromophenol (0.211 mL, 2 mmol) and phenylboronic acid (490 mg, 4 mmol) were added with copper acetate (364 mg, 2 mmol), triethylamine (TEA, 1.38 mL, 10 mmol) and 4A molecular sieves in dichloromethane (DCM, 25 mL). The reaction mixture was stirred at room temperature for 18 hours. After completion of the reaction, the slurry was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The concentrate was diluted with ethyl acetate (EtOAc) and sodium bicarbonate (NaHCO3) solution for extraction. The organic phase was washed with brine and dried with anhydrous magnesium sulfate (MgSO4). The crude product was purified by fast column chromatography (eluent: hexane) to afford the target product 2-bromodiphenyl ether (232 mg, 47% yield) as a colorless oil. The product was detected by thin-layer chromatography (TLC) with an Rf value of 0.75 (unfolding agent: DCM); liquid chromatography-mass spectrometry (LCMS) analysis showed a retention time (U) of 1.3 min (mobile phase: 95% aqueous methanol), and mass-to-charge ratios (m/z) of 246.84 and 248.86 (MH+); high performance liquid chromatography (HPLC) analysis showed a retention time (U ) was 2.88 min (mobile phase: 90% aqueous acetonitrile) and the purity was 98%. Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, CDCl3, 270 MHz) data: δ 6.95-7.04 (4H, m, ArH), 7.11 (1H, td, J = 1.1, 8.0 Hz, ArH), 7.22-7.37 (3H, m, ArH), 7.61-7.65 (1H, m, ArH). Nuclear magnetic resonance carbon spectroscopy (13C NMR, CDCl3, 68 MHz) data: 115.0 (ArC), 118.2, 120.7, 123.5, 125.1, 128.8, 129.9, 133.9 (ArCH), 153.8, 156.9 (ArC). |
[References]
[1] Patent: WO2009/66072, 2009, A2. Location in patent: Page/Page column 99
[2] Patent: US2014/228568, 2014, A1. Location in patent: Paragraph 0162-0163
[3] Journal of Medicinal Chemistry, 2004, vol. 47, # 3, p. 744 - 755
[4] Patent: WO2014/100695, 2014, A1. Location in patent: Paragraph 00386 |