Hydrogen Bromide → HCID 22329485, compound

Temperature

0 °C

4-Fluoro-3-(5-fluoropyridin-2-yl)phenylamine (1.2 g) was dissolved in 1,4-dioxane (4 ml) and 48% aqueous hydrobromic acid (30 ml). The solution was cooled to 0° C. A solution of sodium nitrite (478 mg) in water (6 ml) was added dropwise with stirring to maintain an internal temperature below 4° C. The mixture was then aged a further 1 h at 4° C. A solution of copper(I) bromide (2.58 g) in 48% aqueous hydrobromic acid (10 ml) was then added slowly to retain a reaction temperature below 5° C. The resulting mixture was then stirred at 5-10° C. for 1 h, ambient temperature for 0.5 h and then heated at 50° C. for 0.5 h. The mixture was then cooled to 4° C., and made basic by addition of 4N aqueous sodium hydroxide (106 ml), followed by 30% aqueous ammonium hydroxide (40 ml). The mixture was extracted with ethyl acetate, the organic phase dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The residue was chromatographed on silica gel eluting with dichloromethane containing 30% isohexane to afford 2-(5-bromo-2-fluorophenyl)-5-fluoropyridine: δH (400 MHz, DMSO) 8.74 (1H, dd, J 2 and 1), 8.05 (1H, dd, J 7 and 3), 7.90 (2H, m), 7.69 (1H, m), 7.38 (1H, dd, J 11 and 9); m/z (ES+) 270, 272.

1. temperatureto maintain an internal temperature below 4° C
2. customa reaction temperature below 5° C
3. stirringThe resulting mixture was then stirred at 5-10° C. for 1 h, ambient temperature for 0.5 h
4. temperatureheated at 50° C. for 0.5 h
5. temperatureThe mixture was then cooled to 4° C.
6. extractionThe mixture was extracted with ethyl acetate
7. dry with materialthe organic phase dried over anhydrous sodium sulfate
8. filtrationfiltered
9. customevaporated to dryness
10. customThe residue was chromatographed on silica gel eluting with dichloromethane containing 30% isohexane

ORD record

ord-26c75227a6864eb59de13ecd64685930

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06900215B2