4-Methylmorpholine → HCID 15512823, Verbindung

HRID 1978833Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1978833
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:14][CH3:15])=[C:6]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH:7]=1.[CH3:16][N:17]([CH:25]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:26](O)=[O:27])[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O.O.CCOC(C)=O>[C:21]([O:20][C:18](=[O:19])[N:17]([C@H:25]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:26]([N:11]1[CH2:12][CH2:13][CH:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:14][CH3:15])[CH2:9][CH2:10]1)=[O:27])[CH3:16])([CH3:24])([CH3:22])[CH3:23]

Komponenten

9

Edukt 5

HCID 79724-MethylmorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 52406092-{[(Tert-butoxy)carbonyl](methyl)amino}-3-phenylpropanoic acidHCID 155128224-(5-Fluoro-2-methoxyphenyl)piperidine2×

Produkt 1

HCID 15512823HCID 15512823, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

The above product of 4-(5-fluoro-2-methoxy-phenyl)-piperidine (Intermediate 4) was dissolved in N,N-dimethylformamide (10 mL) at 0° C. To the resulting solution, 0.70 g (2.5 mmole) of 2-[N-methyl-N-(tert-butoxycarbonyl)-amino]-3-phenyl-propionic acid in a minimal amount of DMF was added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (DAEC) (0.48 g, 2.5 mmole), 1-hydroxybenzotriazole hydrate (HOBT) (0.41 g, 2.5 mmole) and 4-methylmorpholine (NMM) (0.37 mL, 3.4 mmole) and the mixture was stirred overnight (the reaction temperature was slowly allowed to warm up to room temperature). The reaction mixture was diluted with water (50 mL) and EtOAc (50 mL) and the layers separated. The aqueous layer was washed with HCl (1N), saturated NaHCO3, and the combined aqueous layers were extracted three times with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. Flash chromatography, gradient elution with 1:4 EtOAc-hexane to 3:7 EtOAc-hexane to afford (R)-{1-benzyl-2-[4-(5-fluoro-2-methoxy-phenyl)-piperidin-1-yl]-2-oxo-ethyl}-methyl-carbamic acid tert-butyl ester as a yellow oil.

Aufarbeitung

  1. customthe layers separated
  2. washThe aqueous layer was washed with HCl (1N), saturated NaHCO3
  3. extractionthe combined aqueous layers were extracted three times with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. washFlash chromatography, gradient elution with 1:4 EtOAc-hexane to 3:7 EtOAc-hexane

Quellen und Nachweise

ORD-Eintrag
ord-31617493c91a4427ba2ff567ac61795b
Quelldatensatz
uspto-grants-2001_05
Patentnummer
US06239126B1

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