Synthesis
Step-1: Synthesis of 3-bromo-5-hydroxybenzaldehyde: 2.5 M n-butyllithium (n-BuLi, 7.9 mL, 19.84 mmol) was slowly added dropwise to a solution of 3,5-dibromophenol (2.5 g, 9.92 mmol) in tetrahydrofuran (THF, 25 mL) at -78°C for a controlled time of 15 min. The reaction mixture was continued to be stirred at -78 °C for 20 min, followed by dropwise addition of dry N,N-dimethylformamide (DMF, 15.29 mL, 198.4 mmol). After maintaining the reaction at -78 °C for 30 min, the reaction mixture was warmed up to room temperature and stirred for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated ammonium chloride solution (200 mL) and extracted with ethyl acetate (EtOAc, 3 x 250 mL). The organic layers were combined, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (100-200 mesh, eluent: 0-6% hexane solution of ethyl acetate) to afford the target compound 3-bromo-5-hydroxybenzaldehyde (1.0 g, 50.12% yield) as a white solid. Nuclear magnetic resonance hydrogen spectrum (1H NMR, 400 MHz, DMSO-d6): δ (ppm): 10.5 (broad peak, 1H), 9.85 (single peak, 1H), 7.50 (single peak, 1H), 7.25 (double peak, 2H).
References
[1] Patent: WO2015/184405, 2015, A1. Location in patent: Paragraph 0135; 0141; 0148; 0154; 0160; 0166; 0173; 0184
[2] Angewandte Chemie - International Edition, 2017, vol. 56, # 49, p. 15746 - 15750
[3] Angew. Chem., 2017, vol. 129, p. 15952 - 15957,6
[4] Patent: WO2018/114965, 2018, A1. Location in patent: Page/Page column 26
[5] Patent: WO2008/58387, 2008, A1. Location in patent: Page/Page column 20
