Reaction #43408

Reaction equation

1,1-dimethylethyl [2-chloro-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

caesium fluoride

tributyl[1-(ethyloxy)ethenyl]stannane

potassium fluoride

→

1,1-Dimethylethyl [2-[1-(ethyloxy)ethenyl]-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate

Solvents

1,4-dioxane

Conditions

Workup

1. 1
   Filtrationthe mixture was filtered through Kieselguhr
2. 2
   Washwashing with 1,4-dioxane
3. 3
   workup.ADDITIONEthyl acetate and water were added to the filtrate
4. 4
   OtherThe phases were separated
5. 5
   Extractionthe aqueous phase extracted twice with ethyl acetate
6. 6
   DryingThe combined organic extracts were dried over magnesium sulphate
7. 7
   Otherevaporated
8. 8
   OtherThe residue was rapidly chromatographed
9. 9
   Washeluting with 25-50% dichloromethane in hexane affording the product as a light brown oil (22.2 g, 99%)

Procedure

A degassed solution of 1,1-dimethylethyl [2-chloro-5-fluoro-6-(methyloxy)-3-pyridinyl]carbamate (20 g, 72.2 mmol) in 1,4-dioxane (200 ml) was treated with bis(tri-tert-butylphosphine) palladium(0) (1.05 g), caesium fluoride (21.93 g) and tributyl[1-(ethyloxy)ethenyl]stannane (26.9 ml) then heated to 100° C. overnight. The cooled mixture was treated with 10% aqueous potassium fluoride solution. After 0.5 hour stirring, the mixture was filtered through Kieselguhr, washing with 1,4-dioxane. Ethyl acetate and water were added to the filtrate. The phases were separated and the aqueous phase extracted twice with ethyl acetate. The combined organic extracts were dried over magnesium sulphate and evaporated. The residue was rapidly chromatographed eluting with 25-50% dichloromethane in hexane affording the product as a light brown oil (22.2 g, 99%).

Source