Réaction #313153

Équation de réaction

DIC

acetic acid

[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid

Intermediate 7

[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl]acetic acid

N′-hydroxyethanimidamide

→

(3EZ,5S)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one O-methyloxime

Rendement 102.4%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   FiltrationThe precipitate was filtered
2. 2
   Concentrationthe solution was concentrated in vacuo
3. 3
   workup.ADDITIONPyridine (1 ml) was added
4. 4
   workup.STIRRINGthe reaction mixture was stirred
5. 5
   Températureat reflux overnight The solvent
6. 6
   Autrewas removed
7. 7
   workup.ADDITIONdichloromethane was added
8. 8
   LavageThe organic phase was washed with HCl 1N
9. 9
   SéchageThe organic phase was dried (MgSO4)
10. 10
    Concentrationconcentrated
11. 11
    Autrepurified on silica gel column chromatography (Ethyl acetate/cyclohexane, 40:60)

Mode opératoire

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%

Source