反应详情

64 g of 60% sodium hydride was added to 200 ml of tetrahydrofuran, and, while the mixed solution was stirred and cooled on ice, a solution obtained by dissolving 258 g of diethyl malonate in 400 ml of tetrahydrofuran was dropped to the mixed solution through 1 hour and 40 minutes so that the reaction temperature was kept below 20° C. Then, while the reaction solution was stirred and cooled on ice, 200 ml of tetrahydrofuran solution dissolving 142 g of 2,3,4-trifluoronitrobenzene was dropped to the reaction solution through 2 hours so that the reaction temperature was kept below 10° C. After reacting at room temperature for 2 hours, 100 ml of acetic acid was added to the reaction solution and tetrahydrofuran was removed by distillation. To the residue, 1 l of chloroform, 1.5 l of water and 100 ml of concentrated hydrochloric acid were added, and the solution was separated. The organic layer was separated from the solution, and the solvent was removed by distillation. To the residue, 250 ml of 4N hydrochloric acid and 200 ml of acetic acid were added, and the solution was heated under reflux for 11 hours. After removing 150 ml of content solution by distillation, 50 ml of acetic acid and 50 ml of water were added to the solution, and the solution was heated under reflux for 31 hours. After the solution was air-cooled, the precipitated crystal was filtered off, washed with diisopropyl ether and was dissolved in 400 ml of methanol. After treating with active carbon, the solvent was removed by distillation. The precipitated crystal was dispersed in diisopropyl ether and was filtered off to obtain 100 g of the subject compound (1) in a 56% yield.

1. temperaturecooled on ice
2. customa solution obtained
3. additionwas dropped to the mixed solution through 1 hour and 40 minutes so that the reaction temperature
4. customwas kept below 20° C
5. stirringThen, while the reaction solution was stirred
6. additionwas dropped to the reaction solution through 2 hours so that the reaction temperature
7. customwas kept below 10° C
8. customwas removed by distillation
9. additionTo the residue, 1 l of chloroform, 1.5 l of water and 100 ml of concentrated hydrochloric acid were added
10. customthe solution was separated
11. customThe organic layer was separated from the solution
12. customthe solvent was removed by distillation
13. additionTo the residue, 250 ml of 4N hydrochloric acid and 200 ml of acetic acid were added
14. temperaturethe solution was heated
15. temperatureunder reflux for 11 hours
16. customAfter removing 150 ml of content solution
17. distillationby distillation, 50 ml of acetic acid and 50 ml of water
18. additionwere added to the solution
19. temperaturethe solution was heated
20. temperatureunder reflux for 31 hours
21. temperatureAfter the solution was air-cooled
22. filtrationthe precipitated crystal was filtered off
23. washwashed with diisopropyl ether
24. dissolutionwas dissolved in 400 ml of methanol
25. additionAfter treating with active carbon
26. customthe solvent was removed by distillation
27. additionThe precipitated crystal was dispersed in diisopropyl ether
28. filtrationwas filtered off