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0 °C

A warm solution of 4-fluoro-3-(pyridin-3-yl)phenylamine (3.64 g, 19.3 mmol) in 1,4-dioxane (10 ml) was treated with a solution of 48% aqueous hydrobromic acid (100 ml). The resulting suspension was cooled to 0° C. before being treated dropwise over 20 min with a solution of sodium nitrite (1.53 g, 22.2 mmol) in water (4 ml). After stirring at 0° C. for 2 h, a cooled (0° C.) solution of copper(I) bromide (8.31 g, 57.9 mmol) in 48% aqueous hydrobromic acid (30 ml) was added to the reaction which was stirred at 0° C. for 10 min then heated at 50° C. for 20 min. The reaction was cooled to ambient temperature, poured onto ice-cold concentrated ammonia (500 ml) and the product was extracted into ethyl acetate (500 ml). The organics were washed with water (300 ml) and brine (300 ml), dried (Na2SO4), filtered and concentrated in vacuo to give a dark oil. Purification by dry flash column chromatography (silica gel, 10-30% EtOAc/isohexane) gave 3-(5-bromo-2-fluorophenyl)pyridine (3.1 g, 64%) as a white solid: 1H NMR (360 MHz, CDCl3) δ 7.09 (1H, dd, J 9, 1 Hz), 7.37-7.40 (1H, m), 7.46-7.51 (1H, m), 7.56-7.59 (1H, m), 7.83-7.86 (1H, m), 8.63-8.65 (1H, m), 8.77-8.79 (1H, m).

1. additionwas added to the reaction which
2. stirringwas stirred at 0° C. for 10 min
3. temperaturethen heated at 50° C. for 20 min
4. temperatureThe reaction was cooled to ambient temperature
5. additionpoured onto ice-cold concentrated ammonia (500 ml)
6. extractionthe product was extracted into ethyl acetate (500 ml)
7. washThe organics were washed with water (300 ml) and brine (300 ml)
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give a dark oil
12. customPurification
13. dry with materialby dry flash column chromatography (silica gel, 10-30% EtOAc/isohexane)