Ammonia → HCID 11680823, compound

Temperature

-10 °C

To 3-(3,5-difluoropyridin-2-yl)-4-fluorophenylamine was added 1,4-dioxane (5 ml) and 48% aqueous hydrogen bromide (15 ml). The solution was cooled to −10° C., and a solution of sodium nitrite (0.252 g) in water (1 ml) was added dropwise with stirring to maintain an internal temperature below −5° C. The mixture was then stirred for a further 1 h at 0 to −5° C., then a solution of copper(I) bromide (1.283 g) in 48% aqueous hydrogen bromide (5 ml) was added slowly with stirring to maintain a reaction temperature below 10° C. The mixture was then stirred at 10° C. for 1 h, room temperature for a further hour, and then heated at 35° C. for 0.5 h. The reaction mixture was then cooled in an ice bath and 4 N aqueous sodium hydroxide (41 ml) was added slowly with stirring, followed by 30% aqueous ammonia (15 ml). The resulting mixture was extracted with ethyl acetate. The organic extracts were evaporated and the residue subjected to chromatography (silica gel, 10% Et2O/isohexane) to afford 2-(5-bromo-2-fluorophenyl)-3,5-difluoropyridine (0.48 g) as a colourless solid: MS (ES+) m/z 288, 290 [M+H]+.

1. temperatureto maintain an internal temperature below −5° C
2. stirringThe mixture was then stirred for a further 1 h at 0 to −5° C.
3. stirringwith stirring
4. temperatureto maintain a reaction temperature below 10° C
5. stirringThe mixture was then stirred at 10° C. for 1 h, room temperature for a further hour
6. temperatureheated at 35° C. for 0.5 h
7. temperatureThe reaction mixture was then cooled in an ice bath
8. stirringwith stirring
9. extractionThe resulting mixture was extracted with ethyl acetate
10. customThe organic extracts were evaporated

ORD record

ord-8607da07f0c74f01ad5a2ea155b328af

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936608B2