Morpholine → N-[[3-[3-fluoro-4-[4-[3-(4-morpholinyl)-1-oxopropyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide

HRID 1078531

Reaktionsgleichung

Reaktionsgleichung von HRID 1078531
[N:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.N1CCOCC1.C(OCC)(=O)C=C.C1(N=C=NC2CCCCC2)CCCCC1.[F:40][C:41]1[CH:42]=[C:43]([N:53]2[CH2:57][C@H:56]([CH2:58][NH:59][C:60](=[O:62])[CH3:61])[O:55][C:54]2=[O:63])[CH:44]=[CH:45][C:46]=1[N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>CN(C)C1C=CN=CC=1.O1CCCC1.ClCCl.C(O)C>[F:40][C:41]1[CH:42]=[C:43]([N:53]2[CH2:57][CH:56]([CH2:58][NH:59][C:60](=[O:62])[CH3:61])[O:55][C:54]2=[O:63])[CH:44]=[CH:45][C:46]=1[N:47]1[CH2:52][CH2:51][N:50]([C:9](=[O:11])[CH2:8][CH2:7][N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)[CH2:49][CH2:48]1

Komponenten

9

Edukt 5

HCID 8083MorpholineHCID 8821Ethyl AcrylateHCID 10868DicyclohexylcarbodiimideHCID 4108133-(Morpholin-4-yl)propanoic acidHCID 10520848(S)-N-((3-(3-fluoro-4-(piperazin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide

Produkt 1

HCID 21462637N-[[3-[3-fluoro-4-[4-[3-(4-morpholinyl)-1-oxopropyl]-1-piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamideAusbeute 95 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 702EthanolLösungsmittelHCID 21919333Tetrahydrofurane dichloromethaneLösungsmittel

Versuchsvorschrift

3-(4-Morpholinyl)propionic acid (0.600 g, 2.11 mmol), prepared by condensation of morpholine with ethyl acrylate (3 equivalents) in refluxing ethanol, followed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization, was combined with 1,3-dicyclohexylcarbodiimide (0.434 g, 2.11 mmol), 4-(dimethylamino)pyridine (13 mg, 0.11 mmol), (S)-N-[[3-[3-fluoro-4-(1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (0.354 g, 1.05 mmol), and 1:1 tetrahydrofuran/dichloromethane (50 mL) at room temperature. After 3 days the reaction mixture was filtered to remove the precipitated 1,3-dicyclohexylurea and the filtrate concentrated in vacuo. The crude product was chromatographed over silica gel (20 g), eluting with a gradient of 1-6% methanol/chloroform, to give 0.446 g (95%) of the title compound as a white solid with mp 209°-210° C. ##STR12##

Aufarbeitung

  1. distillationfollowed by distillation, saponification (1N aqueous sodium hydroxide, tetrahydrofuran, reflux), neutralization (1N HCl) and lyophilization
  2. filtrationAfter 3 days the reaction mixture was filtered
  3. customto remove the precipitated 1,3-dicyclohexylurea
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe crude product was chromatographed over silica gel (20 g)
  6. washeluting with a gradient of 1-6% methanol/chloroform

Quellen und Nachweise

ORD-Eintrag
ord-aa7de4649cc44da494795db35a686cc8
Quelldatensatz
uspto-grants-1996_08
Patentnummer
US05547950

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