Synthesis
Method 2: Sodium borohydride (1.2 g, 31.7 mmol) was added to a flask containing tetrahydrofuran (THF) (40 mL) under nitrogen protection and stirring was initiated. Subsequently, 4-biphenylacetic acid (5.0 g, 23.6 mmol) was added slowly over 20 min, maintaining the temperature of the reaction mixture at 20-30 °C. After adding THF rinse solution (5 mL), stirring was continued for 20 min. Next, a THF (10 mL) solution of iodine (2.9 g, 11.4 mmol) was added slowly and dropwise over about 1 hour while maintaining the reaction temperature at 20-30 °C. The reaction mixture continued to be stirred at this temperature for about 1 h until thin layer chromatography (TLC) analysis confirmed complete conversion of 4-biphenylacetic acid. Reaction quenching was achieved by addition of 5 wt% aqueous sodium hydroxide solution (26 mL). After thorough mixing, the solution was allowed to partition and the lower aqueous phase was discarded. The aqueous phase was extracted with isopropyl acetate (2 x 25 mL) and the organic phases were combined and washed with deionized water (4 x 20 mL). The organic phase was evaporated under reduced pressure to give 2-(biphenyl-4'-yl)ethanol as a light yellow crystalline solid (4.6 g, 98.5% yield). The product can also be purified by crystallization via solvent exchange of isopropyl acetate with heptane as described in Method 1.
References
[1] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 15, p. 4740 - 4749
[2] Patent: WO2008/48609, 2008, A1. Location in patent: Page/Page column 86
[3] Patent: WO2008/5338, 2008, A1. Location in patent: Page/Page column 101
[4] Patent: WO2008/48609, 2008, A1. Location in patent: Page/Page column 55
[5] Patent: WO2014/144836, 2014, A2. Location in patent: Paragraph 0519; 0520
