反应详情

To the THF solution of 3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid methyl ester (2.8 g, 7 mmol) was added cyclopropanyl carbonyl chloride (0.72 ml, 8 mmol) dropwise. The reaction mixture was then heated to reflux for 1 hour. The solvent was removed under vacuo. The mixture was dissolved in EtOAc (50 ml) and washed with water (50 ml×2). The organic layer was dried over Na2SO4 and concentrated under vacuo. The resulted solid was stirred with ether (20 ml) for 1 hour and filtered to give a total of 2.5 g (77% yield) white solid which was used in the next step without further purification.

1. temperatureThe reaction mixture was then heated
2. temperatureto reflux for 1 hour
3. customThe solvent was removed under vacuo
4. dissolutionThe mixture was dissolved in EtOAc (50 ml)
5. washwashed with water (50 ml×2)
6. dry with materialThe organic layer was dried over Na2SO4
7. concentrationconcentrated under vacuo
8. filtrationfiltered