反应详情

温度

-78 °C

To a solution of 1.28 g of N,N,N',N'-tetramethylethylene-diamine in 25 ml of tetrahydrofuran was added 10.5 ml of 1.05 M cyclohexane solution of sec-butyl lithium under a nitrogen gas atmosphere, and a solution of 1.77 g of N,N-diethylbenzamide in 15 ml of tetrahydrofuran was added to the solution at -78° C. After stirring for 10 minutes at -78° C., a solution of 2.24 g of 4-dimethylaminobenzaldehyde in 10 ml of tetrahydrofuran was added to the mixture. After stirring at -78° C. for 1.5 hours, the temperature was gradually elevated to 5° C. and the reaction mixture was concentrated under reduced pressure. To the residue were added 50 ml of water and 50 ml of ethyl ether, and pH of the mixture was adjusted to 0.5 with 4N-hydrochloric acid. After shaking, the organic layer was discarded and 50 ml of methylene chloride was added to the aqueous layer. The pH was adjusted to 12 with 10N-sodium hydroxide solution. After shaking, the aqueous layer was discarded and the organic layer was washed with saturated aqueous sodium chloride solution. After drying over anhydrous sodium sulfate, the organic layer was concentrated under reduced pressure. The crude product obtained was subjested to silica gel column chromatography (eluting solvent, ethyl acetate:hexane:triethylamine=50:50:5). A fraction eluted secondly was concentrated under reduced pressure and the concentrate was tritylated with methyl alcohol to give 0.54 g of 3-(4-dimethylaminophenyl)-1,3-dihydro-isobenzofuran-1-one (Compound A).

1. stirringAfter stirring at -78° C. for 1.5 hours
2. customwas gradually elevated to 5° C.
3. concentrationthe reaction mixture was concentrated under reduced pressure
4. additionTo the residue were added 50 ml of water and 50 ml of ethyl ether, and pH of the mixture
5. stirringAfter shaking
6. addition50 ml of methylene chloride was added to the aqueous layer
7. stirringAfter shaking
8. washthe organic layer was washed with saturated aqueous sodium chloride solution
9. dry with materialAfter drying over anhydrous sodium sulfate
10. concentrationthe organic layer was concentrated under reduced pressure
11. customThe crude product obtained
12. washwas subjested to silica gel column chromatography (eluting solvent, ethyl acetate:hexane:triethylamine=50:50:5)
13. washA fraction eluted secondly
14. concentrationwas concentrated under reduced pressure