Reaktion #313153

Reaktionsgleichung

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

Ausbeute 102.4%

Lösungsmittel

dichloromethane

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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%

Quelle