反应详情

20 ml of acetic anhydride and 6 ml of ethyl orthoformate were added to the whole of the ethyl 3-difluoromethoxy-2,4,5-trifluorobenzoylacetate [(XV), R1 =--OCHF2, R3' =H, R17 =C2H5, X=X'=F] prepared as described in step (b) above, and, after the mixture had been heated under reflux for 2 hours, the excess acetic anhydride and ethyl orthoformate were removed by evaporation under reduced pressure. The residue was dissolved in 200 ml of methylene chloride, and 1.25 g (0.022 moles) of cyclopropylamine was added dropwise, whilst stirring and ice-cooling; the stirring was continued, whilst ice-cooling, for an additional 1 hour. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was subjected to silica gel column chromatography, using a 9:1 by volume mixture of toluene and ethyl acetate as the eluent, to give 3.29 g of ethyl 3-cyclopropylamino-2-(3-difluoromethoxy-2,4,5-trifluorobenzoyl)acrylate as an amber colored liquid.

1. custom' =H, R17 =C2H5, X=X'=F] prepared
2. temperaturehad been heated
3. temperatureunder reflux for 2 hours
4. customthe excess acetic anhydride and ethyl orthoformate were removed by evaporation under reduced pressure
5. dissolutionThe residue was dissolved in 200 ml of methylene chloride
6. temperatureice-cooling
7. temperaturecooling, for an additional 1 hour
8. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
9. additionby volume mixture of toluene and ethyl acetate as the eluent