Reaction #1519102

Reaction equation

4-chloropyridine-2-carboxylic acid ethyl ester

ethyl acetate

sodium hydride

hydrochloric acid

→

3-(4-chloropyrid-2-yl)-3-oxopropionic acid ethyl ester

Yield 88.5%

Solvents

tetrahydrofuran

tetrahydrofuran

n-hexane

Conditions

Workup

1. 1
   OtherWhen the exothermic reaction
2. 2
   Otherthe reaction
3. 3
   Concentrationthe solution is concentrated to half its volume
4. 4
   ExtractionExtraction
5. 5
   Dryingdried (sodium sulfate)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated

Procedure

Under a nitrogen atmosphere, 4 g (approximately 60% dispersion in paraffin oil, about 100 mmol) of sodium hydride are washed twice with 60 ml of n-hexane each time, and then 400 ml of absolute tetrahydrofuran are added. The mixture is heated to 50° C. and, in the course of 2 hours, a solution of 13.36 g (72 mmol) of 4-chloropyridine-2-carboxylic acid ethyl ester and 10.04 g (114 mmol) of ethyl acetate in 60 ml of absolute tetrahydrofuran is added dropwise, during which the mixture begins to boil vigorously. When the exothermic reaction has subsided, stirring is carried out for 12 hours at room temperature to complete the reaction. The yellow suspension is poured into 400 ml of ice-water and rendered neutral with 15% hydrochloric acid, and the solution is concentrated to half its volume. Extraction is then carried out twice with 200 ml of ethyl acetate each time, and the organic extracts are combined, dried (sodium sulfate), filtered and concentrated. 14.5 g of 3-(4-chloropyrid-2-yl)-3-oxopropionic acid ethyl ester are obtained in the form of a light-brown oil, which is used for further syntheses without further purification.

Source