Borane → 4-Bromo-2-fluorobenzeneethanol

Temperature

0 °C

4-Bromo-2-fluoro-phenyl-acetic acid (36 g, 154 mmol) (40.6 g, 174 mmol) was dissolved in THF (100 mL), and cooled to 0° C. in an ice-bath. Borane (1 M in THF, 200 mL, 1.2 eq) was then added dropwise. During the addition, the temperature rose slowly to 27° C. After complete addition the ice-bath was removed and the reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was added carefully to saturated aqueous K2CO3 (300 mL), and the obtained suspension was diluted with H2O (500 mL). The THF layer was separated and concentrated under reduced pressure. The aqueous layer was extracted with EtOAc (2×100 mL). The residue from the concentrated THF layer was dissolved into the combined organic layers, which was washed with brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure, yielding crude material (35.6 g) as a yellow oil, which solidified to a white solid upon standing. The crude material was purified by column chromatography (SiO2; 1750 mL, 0-5% MeOH in CH2Cl2), yielding the title compound as a white solid (31.5 g, 144 mmol, 82%). 1H-NMR (CDCl3, 300 MHz): 1.50 (s, 1H); 2.95 (t, 2H); 3.92 (t, 2H); 7.18 (t, 1H); 7.28 (m, 1H)