Reaction #531831

Reaction equation

8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one

benzoxazinone

8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one

copper(I) cyanide

→

title compound

8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-cyano-4H-3,1-benzoxazin-4-one

Solvents

ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was then heated
2. 2
   Temperatureat reflux overnight
3. 3
   OtherThe reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction
4. 4
   Filtrationfiltered through Celite®
5. 5
   Washby washing three times with 10% aqueous sodium bicarbonate solution
6. 6
   ExtractionThe organic extract
7. 7
   Dryingwas dried (MgSO4)
8. 8
   Concentrationconcentrated under reduced pressure

Procedure

To a solution of 8-chloro-2-[3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6-iodo-4H-3,1-benzoxazin-4-one (i.e. the benzoxazinone product of Step B) (575 mg, 1.1 mmol) in tetrahydrofuran (15 mL) was added copper(I) iodide (840 mg, 0.44 mmol), tetrakis(triphenyphosphine)palladium(0) (255 mg, 0.22 mmol) and copper(I) cyanide (500 mg, 5.5 mmol) sequentially at room temperature. The reaction mixture was then heated at reflux overnight. The reaction turned black in color, at which point thin layer chromatography on silica gel confirmed completion of the reaction. The reaction was diluted with ethyl acetate (20 mL) and filtered through Celite®, followed by washing three times with 10% aqueous sodium bicarbonate solution and once with brine. The organic extract was dried (MgSO4) and concentrated under reduced pressure to afford 375 mg of the title compound as a crude yellow solid.

Source