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 dichloromethane (3 ml) was added N′-hydroxyethanimidamide (12 mg, 0.16 mmol) followed by DIC (36 mg, 0.28 mmol). The reaction mixture was stirred 1 h30. The precipitate was filtered and the solution was concentrated in vacuo. Pyridine (1 ml) was added and the reaction mixture was stirred at reflux overnight The solvent was removed and dichloromethane was added. The organic phase was washed with HCl 1N then NaHCO3. The organic phase was dried (MgSO4), concentrated and purified on silica gel column chromatography (Ethyl acetate/cyclohexane, 40:60) to afford (3EZ,5S)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one O-methyloxime (56 mg). Yield: 91%. HPLC purity: 90%

1. filtrationThe precipitate was filtered
2. concentrationthe solution was concentrated in vacuo
3. additionPyridine (1 ml) was added
4. stirringthe reaction mixture was stirred
5. temperatureat reflux overnight The solvent
6. customwas removed
7. additiondichloromethane was added
8. washThe organic phase was washed with HCl 1N
9. dry with materialThe organic phase was dried (MgSO4)
10. concentrationconcentrated
11. custompurified on silica gel column chromatography (Ethyl acetate/cyclohexane, 40:60)