Hydrogen Bromide → HCID 11543355, Verbindung

Temperatur

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 organic extract was washed with water (300 ml) and brine (300 ml), dried over anhydrous sodium sulfate, 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. extractionThe organic extract
8. washwas washed with water (300 ml) and brine (300 ml)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customto give a dark oil
13. customPurification
14. dry with materialby dry flash column chromatography (silica gel, 10-30% EtOAc/isohexane)

ORD-Eintrag

ord-2c31e35f2b8c4ded89014040f8cc3c01

Quelldatensatz

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06936608B2