反应详情

Ethyl 3-ethoxy-2-(2',6'-dichloro-5'-fluoronicotinoyl)-acrylate prepared from 1.25 g of ethyl 2,6-dichloro-5-fluoronicotinoylacetate by a conventional process was dissolved in 10 ml of methanol. To the methanol solution, 1.30 g of N-ethoxycarbonyl-2,4-difluoro-m-phenylenediamine methansulfonate of Reference Example 8 was added together with 500 mg of triethylamine. The reaction solution was concentrated in vacua. To the residue were added 50 ml of chloroform and 50 ml of distilled water. After shaking, the mixture was separated into layers. The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacua. To the residue were added 2.1 g of anhydrous potassium carbonate and 4 ml of N,N-dimethylformamide. The solution was heated and stirred at 90° C. for 15 minutes. The reaction solution was allowed to cool down and 50 ml of chloroform and 300 ml of distilled water were added, followed by separation. The chloroform layer was washed twice with 300 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated in vacua. The precipitate was dispersed in ethanol, collected by filtration and washed with ethanol and then diisopropyl ether to give 647 mg of the title compound.

1. concentrationThe reaction solution was concentrated in vacua
2. additionTo the residue were added 50 ml of chloroform and 50 ml of distilled water
3. customthe mixture was separated into layers
4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
5. concentrationconcentrated in vacua
6. additionTo the residue were added 2.1 g of anhydrous potassium carbonate and 4 ml of N,N-dimethylformamide
7. temperatureThe solution was heated
8. stirringstirred at 90° C. for 15 minutes
9. temperatureto cool down
10. addition50 ml of chloroform and 300 ml of distilled water were added
11. customfollowed by separation
12. washThe chloroform layer was washed twice with 300 ml of distilled water
13. dry with materialdried over anhydrous magnesium sulfate
14. concentrationconcentrated in vacua
15. additionThe precipitate was dispersed in ethanol
16. filtrationcollected by filtration
17. washwashed with ethanol