Synthesis
General procedure for the synthesis of (5-bromo-2-iodophenyl)methanol from methyl 5-bromo-2-iodobenzoate: A tetrahydrofuran (THF, 10 mL) solution of methyl 5-bromo-2-iodobenzoate was slowly added to a stirring ethanol (20 mL) solution of sodium borohydride (1.1 g, 14.7 mmol, 2 eq.) at 5 °C. The reaction system was gradually warmed to room temperature and stirred continuously under nitrogen protection for 18 hours. Subsequently, sodium borohydride (0.84 g, 22 mmol, 1.5 eq.) was added by supplementation and the reaction was continued with stirring for 22 hours. Upon completion of the reaction, the mixture was cooled to 0 °C and the reaction was quenched by slow dropwise addition of 15% aqueous citric acid solution (10 mL). The reaction mixture was extracted with dichloromethane (DCM, 2 x 75 mL) and the organic phases were combined. The organic layer was washed sequentially with 15% aqueous sodium chloride (100 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford the target product (5-bromo-2-iodophenyl)methanol (4.5 g, 100% yield) as a white solid. The product was characterized by NMR hydrogen spectrum (400 MHz, CDCl3): δ 1.83-1.88 (m, 1H), 4.63 (s, 2H), 7.12 (dd, J = 2.8, 8.4 Hz, 1H), 7.62-7.66 (m, 2H).
References
[1] Organic Letters, 2008, vol. 10, # 14, p. 3001 - 3004
[2] Tetrahedron, 2011, vol. 67, # 1, p. 125 - 143
[3] Patent: WO2018/15879, 2018, A1. Location in patent: Page/Page column 81
[4] Patent: US2004/92521, 2004, A1. Location in patent: Page/Page column 19-20; 46
[5] Patent: US2005/256118, 2005, A1. Location in patent: Page/Page column 18-19
