反应详情

温度

60 °C

A mixture of ethyl acetoacetate (72.5 g, 0.56 mol), zinc dust (98 g, 1.51 mol) and anhydrous sodium acetate (102 g, 1.21 mol) in glacial acetic acid (110 mL) was heated to 60° C. Ethyl-2-hydroxyimino-3-oxo-3-phenyl-propanoate (110 g, 0.5 mol) was added as a solution (some precipitation on standing) in glacial acetic acid (550 mL) in 3 portions with vigorous stirring over a period of 1 h. The temperature increased to 90° C. during the addition and the reaction was then maintained at 60-75° C. for 3 h. Additional zinc dust (49 g, 0.75 mol) was added over 15 min, again causing a temperature rise, and then the reaction mixture was then stirred at 60 to 75° C. for 1 h. After cooling to room temperature the mixture was filtered and the filtrate was evaporated in vacuo to give a residue which was azeotroped with toluene (2×200 mL) to remove residual acetic acid. Water (2 L) and ethyl acetate (300 mL) were added to the residue and the mixture was stirred until two clear phases were obtained. The organic phase was separated and the aqueous phase extracted with ethyl acetate (2×200 mL). The combined organic phases were washed successively with water (2×250 mL), saturated bicarbonate solution (2×250 mL), water (2×100 mL), brine (2×100 mL), dried over anhydrous sodium sulfate and then concentrated to give a gummy residue. A mixture of dichloromethane and petroleum ether (175 mL; 1:6) was added to the solid and it was stirred for 15 min. The resulting free-flowing solid was filtered off and washed with chilled petroleum ether (100 mL) to afford diethyl 5-methyl-3-phenyl-1H-pyrrole-2,4-dicarboxylate (85 g, 57%) as an off-white solid.

1. customsome precipitation
2. temperatureThe temperature increased to 90° C. during the addition
3. temperaturethe reaction was then maintained at 60-75° C. for 3 h
4. stirringthe reaction mixture was then stirred at 60 to 75° C. for 1 h
5. temperatureAfter cooling to room temperature the mixture
6. filtrationwas filtered
7. customthe filtrate was evaporated in vacuo
8. customto give a residue which
9. customwas azeotroped with toluene (2×200 mL)
10. customto remove residual acetic acid
11. additionWater (2 L) and ethyl acetate (300 mL) were added to the residue
12. stirringthe mixture was stirred until two clear phases
13. customwere obtained
14. customThe organic phase was separated
15. extractionthe aqueous phase extracted with ethyl acetate (2×200 mL)
16. washThe combined organic phases were washed successively with water (2×250 mL), saturated bicarbonate solution (2×250 mL), water (2×100 mL), brine (2×100 mL)
17. dry with materialdried over anhydrous sodium sulfate
18. concentrationconcentrated
19. customto give a gummy residue
20. additionwas added to the solid and it
21. stirringwas stirred for 15 min
22. filtrationThe resulting free-flowing solid was filtered off
23. washwashed with chilled petroleum ether (100 mL)