反应详情

温度

65 °C

Into a 500 milliliter three-necked round-bottom reaction flask equipped with a mechanical stirrer, thermometer, nitrogen inlet and outlet and oil bath was added 30.0 grams (0.10 mol) of ethyl 3-[(4-bromo-2-methylphenyl)amino]-3-oxopropanoate prepared as in Example A, 34.5 grams (0.25 mol) of anhydrous potassium carbonate, 100 milliliters of anhydrous dimethylformamide and 8.6 milliliters (0.10 mol) of 1,2-dibromoethane. The resulting mixture as stirred under a nitrogen atmosphere at a temperature of 65° C. for a period of 3 hours and then at a temperature of 80° C. for a period of 3.5 hours. Following this period, high pressure liquid chromatographic analysis showed the reaction to be incomplete. An additional 13.8 grams (0.10 mol) of anhydrous potassium carbonate was added and the reaction mixture was stirred at ambient temperature for a period of 16 hours. An additional 1.7 milliliters (0.02 mol) of 1,2-dibromoethane was then added and the reaction mixture was heated at a temperature of 75° C. for a period of 3.5 hours. Anhydrous potassium carbonate (6.0 grams, 0.043 mol) was then added and heating was continued for an additional 2.5 hours. The reaction mixture was then cooled, diluted with methylene chloride and filtered to remove suspended solids. Concentration under reduced pressure gave a brown liquid which was chromatographed on silica gel using 3:1 volume/volume hexane-ethyl acetate as the eluent. Early fractions contained 17.8 grams (55.0 mmol) of 1-(4-bromo-2-methylphenylaminocabonyl)cyclopropanecarboxylate as a pale yellow solid having a melting point of 87.0° C.-90.0° C. The total yield was 56.0 percent based on a 96.7 weight percent assay of the starting ethyl 3-[(4-bromo-2-methylphenyl)amino]-3-oxopropanoate. NMR analysis of the product indicated the following:

1. customInto a 500 milliliter three-necked round-bottom reaction flask equipped with a mechanical stirrer
2. additionthermometer, nitrogen inlet and outlet and oil bath was added
3. waitat a temperature of 80° C. for a period of 3.5 hours
4. waitFollowing this period
5. customthe reaction
6. stirringthe reaction mixture was stirred at ambient temperature for a period of 16 hours
7. temperaturethe reaction mixture was heated at a temperature of 75° C. for a period of 3.5 hours
8. temperatureheating
9. waitwas continued for an additional 2.5 hours
10. temperatureThe reaction mixture was then cooled
11. filtrationfiltered
12. customto remove
13. concentrationConcentration under reduced pressure
14. customgave a brown liquid which
15. customwas chromatographed on silica gel using 3:1 volume/volume hexane-ethyl acetate as the eluent