Synthesis
Step A: To a round bottom flask was added 4-bromobenzaldehyde (69.6 g, 376 mmol), 4-(trifluoromethyl)phenylboronic acid (75.0 g, 395 mmol), and 1-propanol (appropriate amount), and the reaction mixture was stirred for 15 min at 70 °C until a clarified solution was obtained. Triphenylphosphine (888 mg, 3.38 mmol), palladium(II) acetate (256 mg, 1.13 mmol), 2M aqueous sodium carbonate (226 mL, 451 mmol), and water (138 mL) were sequentially added to the resulting solution. The reaction system was heated and refluxed for 1 hour, keeping the system open to air. Upon completion of the reaction, water (900 mL) was added and the reaction mixture was cooled to 7°C. Stirring was continued for 30 minutes until 4'-(trifluoromethyl)biphenyl-4-carbaldehyde was completely precipitated. The precipitate was collected by filtration and the solid was washed with cold water (~600 mL). The solid was dissolved in diethyl ether (500 mL), filtered through a pad of diatomaceous earth and silica, and the filter cake was washed with diethyl ether (2 x 500 mL). The filtrate was concentrated under reduced pressure to give 4'-(trifluoromethyl)biphenyl-4-carbaldehyde (90.0 g, 96% yield) as a pure white solid. The product was confirmed structurally by 1H NMR (400 MHz, CDCl3, δ): 7.75 (s, 4H), 7.76-7.79 (m, 2H), 7.96-8.04 (m, 2H), 10.10 (s, 1H). Mass spectrometry (MS) showed [M + 1] peak at 250.3.
References
[1] Patent: US2012/165343, 2012, A1. Location in patent: Page/Page column 15
[2] Applied Organometallic Chemistry, 2012, vol. 26, # 9, p. 478 - 482
[3] Patent: WO2005/118542, 2005, A1. Location in patent: Page/Page column 43; 55-56
[4] Green Chemistry, 2011, vol. 13, # 1, p. 169 - 177
[5] ChemMedChem, 2016, p. 2194 - 2204
