Synthesis
The general procedure for the synthesis of 4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile from 4-(4-bromo-3-formylphenoxy)benzonitrile was as follows: 100 g of 4-(4-bromo-3-formylphenoxy)benzonitrile (VI) was dissolved in 500 mL of methanol at 25-30 °C, and subsequently cooled to 10-15 °C. While maintaining 10-15 °C, 6.2 g of sodium borohydride was slowly added for 60-90 min. After the addition was completed, the temperature of the reaction system was slowly increased to 15-20°C. Upon completion of the reaction, 1000 mL of water was added to the reaction mixture and stirred at 25-30 °C for 1 hour. The resulting solid product was collected by vacuum filtration, washed with water and dried under vacuum at not more than 55 °C to obtain 4-(4-bromo-3-(hydroxymethyl)phenoxy)benzonitrile (V). Yield: 99.0%; purity: 99.02%.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 8, p. 2129 - 2132
[2] Patent: WO2018/207216, 2018, A1. Location in patent: Page/Page column 10
[3] Patent: CN108659024, 2018, A. Location in patent: Paragraph 0038-0039
[4] Patent: WO2018/115362, 2018, A1. Location in patent: Paragraph 0121
[5] Patent: US2007/293457, 2007, A1. Location in patent: Page/Page column 39-40
