Ammonia → HCID 11680823, compound

Temperature

-10 °C

To the 3-(3,5-difluoropyridin-2-yl)-4-fluorophenylamine prepared above 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 at such a rate as to maintain an internal temperature below −5° C. The mixture was then stirred for a further 1 h at <0° C. before 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. This mixture was then stirred at 10° C. for 1 h, ambient temperature a further 1 h and then heated at 35° C. for 30 min. The reaction mixture was then cooled in an ice-water 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 extract was evaporated and the residue subjected to chromatography on silica gel, eluting with 10% diethyl ether in isohexane, to afford 2-(5-bromo-2-fluorophenyl)-3,5-difluoropyridine (0.48 g) as a colourless solid: m/z (ES+) 288, 290 (MH+).

1. temperatureto maintain an internal temperature below −5° C
2. additionwas added slowly
3. stirringwith stirring
4. temperatureto maintain a reaction temperature below 10° C
5. stirringThis mixture was then stirred at 10° C. for 1 h, ambient temperature a further 1 h
6. temperatureheated at 35° C. for 30 min
7. temperatureThe reaction mixture was then cooled in an ice-water bath
8. stirringwith stirring
9. extractionThe resulting mixture was extracted with ethyl acetate
10. extractionThe organic extract
11. customwas evaporated
12. washeluting with 10% diethyl ether in isohexane

ORD record

ord-d64c25e7841148a89824174871791e6f

Source dataset

uspto-grants-2005_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06960598B2