2-Bromo-5-fluoropyridine

Chemical Properties

Uses

• 5-fluoro-2-phenylpyridine via Suzuki coupling reaction with phenylboronic acid
• 5-fluoro-2-(p-tolyl)pyridine via Suzuki coupling reaction with p-tolylboronic acid

Uses

Synthesis

21717-96-4

41404-58-4

Example C Synthesis of 2-bromo-5-fluoropyridine: 2-Amino-5-fluoropyridine (6.5 g, 58 mmol) was added in batches to 48% hydrobromic acid (28.8 mL, 296 mmol) cooled to 0-5 °C. A solution formed from bromine (8.9 mL, 174 mmol) and sodium nitrite (10 g, 145 mmol) dissolved in 20 mL of water was added slowly and dropwise at 0-5 °C (note: nitrogen release). The reaction mixture was stirred for 1 hour and then quenched with concentrated hydrochloric acid. A 32% sodium hydroxide solution (50.5 mL, 0.55 mol) was then added. The reaction mixture was continued to be stirred for 20 minutes at room temperature and then extracted three times with ether. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure at 30 °C and 500 mbar (note: the product is volatile). The crude product was purified by rapid chromatography on silica gel with an elution gradient of dichloromethane/pentane (0:100 → 50:50). The final product was 2-bromo-5-fluoropyridine (6.7 g, 66% yield) in light yellow solid form.

References