Potassium Cyanide → 2-Bromo-4-chloro-6-fluorobenzonitrile

Temperature

25 °C

To a solution of 2-bromo-4-chloro-6-fluoro-phenylamine (10 g, 44.5 mmol) in anhydrous DCM (100 ml) was added nitrosonium tetrafluoroborate (5.72 g, 49.01 mmol) and the mixture was stirred at 25° C. for 1 h. The reaction mixture was then cooled to 0° C. prior to addition of KCN (5.8 g, 89.1 mmol) followed by a dropwise addition of an aqueous solution (50 ml) of cupric sulfate hexahydrate (22.24 g, 89.1 mmol). After stirring for 40 minutes at 0° C. the reaction mixture was allowed to warm to 25° C. and stirring was continued for 1 h. The reaction mixture was diluted with DCM (100 ml) and slowly quenched by the addition of aqueous saturated solution of NaHCO3 until gas evolution is no longer observed. The resulting heterogeneous mixture was then filtered through a pad of celite and the organic layer was separated, washed twice with brine, dried with Na2SO4 and evaporated. The crude residue thus obtained was purified by chromatography (silica gel; hexane/EtOAc 90:10) to obtain the title compound as reddish solid (4 g, 38%).

1. temperatureThe reaction mixture was then cooled to 0° C.
2. stirringAfter stirring for 40 minutes at 0° C. the reaction mixture
3. temperatureto warm to 25° C.
4. stirringstirring
5. waitwas continued for 1 h
6. customslowly quenched by the addition of aqueous saturated solution of NaHCO3 until gas evolution
7. filtrationThe resulting heterogeneous mixture was then filtered through a pad of celite
8. customthe organic layer was separated
9. washwashed twice with brine
10. dry with materialdried with Na2SO4
11. customevaporated
12. customThe crude residue thus obtained
13. customwas purified by chromatography (silica gel; hexane/EtOAc 90:10)

ORD record

ord-67b4ba064f6a49da8dc617510ef2f2e6

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08912221B2