反应详情

温度

0 °C

A solution of sodium nitrite (1.33 gm) in water (5 cm3) was added dropwise to a cooled solution of ethyl (RS)-2-(2-aminopyrimidin-5-yl)-3-methylbutanoate (1.08 g) in concentrated aqueous hydrochloric acid solution (14.5 cm3), the temperature of the reaction mixture being maintained at less than 5° C. during the addition. The mixture was stirred at 0° C. for 3 hours, then allowed to warm to the ambient temperature and stood for 16 hours. The mixture was then cooled in an ice bath and neutralised by dropwise addition of aqueous potassium carbonate solution (the temperature of the mixture being maintained below 4° C.). The products were extracted into dichloromethane, the organic layers being washed with water and dried over anhydrous magnesium sulphate. Removal of the solvent by evaporation under reduced pressure gave a mixture of two products which was separated by column chromatography on a silica gel support, eluting firstly with dichloromethane containing 2% by volume ethyl acetate to give ethyl (RS)-2-(2-chloropyrimidin-5-yl)- 3-methylbutanoate (0.27 g), Product A, and secondly with dichloromethane containing 10% by volume methanol to give ethyl (RS)-2-(pyrimidin-2-one-5-yl)-3-methylbutanoate, (0.34 g), Product B.

1. temperaturethe temperature of the reaction mixture being maintained at less than 5° C. during the addition
2. temperatureto warm to the ambient temperature
3. waitstood for 16 hours
4. temperatureThe mixture was then cooled in an ice bath
5. temperaturebeing maintained below 4° C.)
6. extractionThe products were extracted into dichloromethane
7. washthe organic layers being washed with water
8. dry with materialdried over anhydrous magnesium sulphate
9. customRemoval of the solvent
10. customby evaporation under reduced pressure
11. customgave
12. additiona mixture of two products which
13. customwas separated by column chromatography on a silica gel support
14. washeluting firstly with dichloromethane containing 2% by volume ethyl acetate