(1) Synthesis of (3-bromo-2-methylphenyl)methanol [99-1] (hereinafter referred to as compound [99-1])
3-Bromo-2-methylbenzoic acid (1.08 g, 5.0 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) and cooled in an ice bath to 0°C. To this solution, sodium borohydride (1.15 g, 30.4 mmol) was added batchwise under stirring. Subsequently, a tetrahydrofuran (16 mL) solution of iodine (3.81 g, 15.0 mmol) was added to the reaction mixture in two slow drops. After addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 20 hours. Upon completion of the reaction, the reaction was quenched by the slow addition of 4N hydrochloric acid (20 mL) under the cooling of the ice bath. The reaction mixture was extracted with ethyl acetate (3 × 20 mL) and the organic phases were combined. The organic phase was washed sequentially with 2N aqueous sodium hydroxide (20 mL) and saturated saline (20 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 4:1) to afford the title compound (3-bromo-2-methylphenyl)methanol (934 mg, 86% yield) as a white solid.
1H-NMR (400 MHz, CDCl3) δ: 7.52-7.50 (1H, m), 7.32 (1H, d, J = 7.6 Hz), 7.06 (1H, t, J = 7.8 Hz), 4.73 (2H, d, J = 5.9 Hz), 2.43 (3H, s), 1.58 (1H, t, J = 5.9 Hz).
