Synthesis
GENERAL METHODS: Borane-tetrahydrofuran complex (BH3-THF, 89 mL, 89.49 mmol) was slowly added dropwise to a stirred solution of 3-fluoro-4-bromobenzoic acid (9.8 g, 44.75 mmol) in tetrahydrofuran (THF, 200 mL) at 25 °C. The dropwise addition was controlled to be completed in 10 min, and the reaction was carried out under nitrogen protection. The reaction mixture was stirred continuously at room temperature for 2 days. Upon completion of the reaction, the reaction was carefully quenched with 2 M sodium carbonate solution (Na2CO3, 200 mL) and subsequently extracted with ether (Et2O, 2 x 500 mL). The organic phases were combined, washed with saturated brine (400 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure to give a pale yellow oil. The crude product was purified by fast silica gel column chromatography, the eluent was a mixture of heptane and ethyl acetate (EtOAc) with a gradient elution ratio of 0 to 70% ethyl acetate. The purified fraction was collected and concentrated to dryness under reduced pressure to give 4-bromo-3-fluorobenzyl alcohol (8.65 g, 94% yield) as a white solid.
References
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[2] Journal of Medicinal Chemistry, 2003, vol. 46, # 14, p. 2973 - 2984
[3] Synlett, 2014, vol. 25, # 1, p. 123 - 127
[4] European Journal of Medicinal Chemistry, 2018, vol. 150, p. 506 - 524
[5] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 10, p. 1257 - 1260
