[Synthesis]
[Example 14] Synthesis of (5-bromo-3-chloropyridin-2-yl)methanol
(1) Dissolve 3-chloro-2,5-dibromopyridine (2.26 g, 8.3 mmol) in toluene (83 mL) under nitrogen protection and cool to -78 °C. A n-hexane solution of 1.6 M n-butyllithium (6.23 mL, 9.96 mmol) was slowly added dropwise, keeping the temperature at -78 °C. After the reaction mixture was stirred at -78 °C for 2 h, anhydrous N,N-dimethylformamide (1.29 mL, 16.6 mmol) was added. Subsequently, the reaction mixture was slowly warmed to room temperature and methanol (83 mL) and sodium borohydride (314 mg, 8.3 mmol) were added. After stirring for 30 min at room temperature, the reaction was quenched by the addition of saturated ammonium chloride solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate = 4/1) to give pale yellow crystalline (5-bromo-3-chloropyridin-2-yl)methanol (967 mg, 52% yield).
1H NMR (CDCl3, 400 MHz): δ= 3.93 (1H, br s), 4.75 (2H, s), 7.86 (1H, d, J=2 Hz), 8.56 (1H, br s). |