Reaction #1435730

Reaction equation

hydrochloric acid

sodium hydride

ethyl 2-chloro-6-fluorophenylacetate

acetic anhydride

→

ethyl (2-chloro-6-fluorophenyl)acetoacetate

Yield 35.8%

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONwere added dropwise
2. 2
   Temperatureunder reflux
3. 3
   Temperaturerefluxed
4. 4
   Temperatureunder heating for 10 hours
5. 5
   TemperatureThe reaction mixture was cooled
6. 6
   Extractionextracted with t-butyl methyl ether
7. 7
   WashThe organic layer was washed with dil. hydrochloric acid, aqueous saturated sodium bicarbonate solution, dil. hydrochloric acid and water
8. 8
   Dryingsubsequently, dried over sodium sulfate
9. 9
   Concentrationconcentrated

Procedure

Into a mixture of 9.6 g of sodium hydride (60% in oil) and 200 ml of tetrahydrofuran, 21.7 g of ethyl 2-chloro-6-fluorophenylacetate were added dropwise under reflux. Then, a solution of 12.3 g of acetic anhydride in 40 ml tetrahydrofuran was added thereto and refluxed under heating for 10 hours. The reaction mixture was cooled, poured into iced dil. hydrochloric acid and extracted with t-butyl methyl ether. The organic layer was washed with dil. hydrochloric acid, aqueous saturated sodium bicarbonate solution, dil. hydrochloric acid and water, subsequently, dried over sodium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give 9.27 g of ethyl (2-chloro-6-fluorophenyl)acetoacetate.

Source