Diisopropylcarbodiimide → (3Ez,5s)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one o-methyloxime

HRID 225971

Reaktionsgleichung

Reaktionsgleichung von HRID 225971
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][C:4]([C:7]([N:9]2[CH2:13][C:12](=[N:14][O:15][CH3:16])[CH2:11][C@H:10]2[CH2:17][C:18](O)=[O:19])=[O:8])=[CH:3][CH:2]=1.O[N:28]=[C:29]([NH2:31])[CH3:30].CC(C)N=C=NC(C)C>ClCCl>[CH3:16][O:15][N:14]=[C:12]1[CH2:11][C@@H:10]([CH2:17][C:18]2[O:19][N:31]=[C:29]([CH3:30])[N:28]=2)[N:9]([C:7]([C:4]2[CH:3]=[CH:2][C:1]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)=[CH:6][CH:5]=2)=[O:8])[CH2:13]1

Komponenten

5

Edukt 3

HCID 12734DiisopropylcarbodiimideHCID 30926N-HydroxyacetamidineHCID 131727525[(2S,4EZ)-1-(biphenyl-4-ylcarbonyl)-4-(methoxyimino)pyrrolidin-2-yl] acetic acid2×

Produkt 1

HCID 131727534(3Ez,5s)-1-(biphenyl-4-ylcarbonyl)-5-[(3-methyl-1,2,4oxadiazol-5-yl)methyl]pyrrolidin-3-one o-methyloximeAusbeute 102,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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%

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-0ac680e44b2a4b5faab3f1a675f39c0c
Quelldatensatz
uspto-grants-2009_07
Patentnummer
US07557136B2

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