4-Bromo-2-phenoxybenzonitrile

Synthesis

Phenol (12.35 g, 131.25 mmol), potassium carbonate (34.55 g, 250 mmol), N,N-dimethylformamide (125 mL), and toluene (125 mL) were added to a three-necked flask fitted with a Dean-Stark splitter and dehydrated by refluxing the flask for 4 h under nitrogen protection until no more water was generated in the reaction system. Subsequently, 100 mL of toluene was removed using a Dean-Stark splitter. After the reaction system was cooled to room temperature, 4-bromo-2-fluorobenzonitrile (25.0 g, 125 mmol) was added and refluxing was continued for 4 hours under nitrogen protection. Upon completion of the reaction, the reaction mixture was diluted by adding toluene (200 mL) and filtered through diatomaceous earth. The filtrate was washed twice with water, dried with anhydrous magnesium sulfate and filtered. The product was purified by silica gel column chromatography (eluent: toluene/ethyl acetate = 9/1). The concentrated sample was rinsed with 200 mL of hexane under ultrasound for 5 min and then filtered. The resulting solid was dried under vacuum at 50 °C for 4 h to give a white solid product (yield: 31.2 g, yield: 91%). The structure of the product was confirmed by 1H-NMR and ESI-MS.1H NMR (500 MHz, CDCl3, δ): 6.97 (s, 1H), 7.11 (d, 2H), 7.25-7.31 (m, 2H), 7.42-7.48 (m, 2H), 7.51 (d, 1H).ESI-MS (m/z) (M+) Calculated value. 272.98, measured value: 273.09.

References

[1] Patent: US9685615, 2017, B2. Location in patent: Page/Page column 85-86
[2] Patent: US2006/135524, 2006, A1. Location in patent: Page/Page column 23
[3] Patent: WO2007/30089, 2007, A1. Location in patent: Page/Page column 85
[4] Angewandte Chemie - International Edition, 2017, vol. 56, # 44, p. 13809 - 13813
[5] Angew. Chem., 2017, vol. 129, # 44, p. 13997 - 14001,5