反应详情

A mixture of 1.620 g (10 mmol) of 2,2,3,3,3-pentafluoropropanimidamide (commercially available) and 2.222 g (10 mmol) of ethyl (2Z)-2-(ethoxymethylidene)-4,4-difluoro-3-oxobutanoate (for preparation see WO 2005/123690) in 10 ml of absolute ethanol is stirred under reflux for 4 days after adding 0.680 g (10 mmol) of sodium methylate. The mixture is then concentrated by evaporation in vacuo and the residue is taken up in 10 ml of water and extracted twice with 10 ml of ethyl acetate. The organic phases are washed successively with 5 ml of water and 5 ml of saturated sodium chloride solution, dried over sodium sulphate, filtered and concentrated by evaporation in vacuo. Chromatographic purification with a mixture of cyclohexane and ethyl acetate gives 1.264 g (3.95 mM, 39.5% of theory) of ethyl 4-(difluoromethyl)-2-(pentafluoroethyl)pyrimidine-5-carboxylate as a white solid.

1. temperatureunder reflux for 4 days
2. concentrationThe mixture is then concentrated by evaporation in vacuo
3. extractionextracted twice with 10 ml of ethyl acetate
4. washThe organic phases are washed successively with 5 ml of water and 5 ml of saturated sodium chloride solution
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. concentrationconcentrated by evaporation in vacuo
8. customChromatographic purification
9. additionwith a mixture of cyclohexane and ethyl acetate