反应详情

To a solution of [(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid (Intermediate 7, 50 mg, 0.14 mmol) in tetrahydrofuran (2 ml) was added CDI (37 mg, 0.23 mmol). The reaction mixture was stirred 1 h30. A solution of N′,3-dihydroxypropanimidamide (16 mg, 0.16 mmol), pyridine (34 ml, 0.14 mmol) in tetrahydrofuran was then added and the reaction mixture was stirred at reflux overnight The solvent was removed and ethyl acetate was added. The organic phase was washed with citric acid 5%, NH4Cl, NaHCO3 then brine. The organic phase was dried (MgSO4), concentrated and purified on silica gel column chromatography (Ethyl acetate) to afford (3EZ,5S)-1-(biphenyl-4-ylcarbonyl)-5-{[3-(2-hydroxyethyl)-1,2,4-oxadiazol-5-yl]methyl}pyrrolidin-3-one O-methyloxime (19 mg). Yield: 27%. HPLC purity: 94%

1. stirringthe reaction mixture was stirred
2. temperatureat reflux overnight The solvent
3. customwas removed
4. additionethyl acetate was added
5. washThe organic phase was washed with citric acid 5%, NH4Cl, NaHCO3
6. dry with materialThe organic phase was dried (MgSO4)
7. concentrationconcentrated
8. custompurified on silica gel column chromatography (Ethyl acetate)