Formaldehyde → 4-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]-1-(morpholinomethyl)piperazin-2-one

HRID 467542Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 467542
C=O.[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[CH2:9]([C:11]1[C:33]([F:34])=[CH:32][C:14]([O:15][C:16]2[CH:30]=[CH:29][C:19]([C:20]([N:22]3[CH2:27][CH2:26][NH:25][C:24](=[O:28])[CH2:23]3)=[O:21])=[CH:18][C:17]=2[F:31])=[C:13]([OH:35])[CH:12]=1)[CH3:10].[C:36](OCC)(=O)C>CO.O.O>[CH2:9]([C:11]1[C:33]([F:34])=[CH:32][C:14]([O:15][C:16]2[CH:30]=[CH:29][C:19]([C:20]([N:22]3[CH2:27][CH2:26][N:25]([CH2:36][N:3]4[CH2:8][CH2:7][O:6][CH2:5][CH2:4]4)[C:24](=[O:28])[CH2:23]3)=[O:21])=[CH:18][C:17]=2[F:31])=[C:13]([OH:35])[CH:12]=1)[CH3:10]

Komponenten

7

Edukt 4

HCID 712Formaldehyde2×HCID 8083Morpholine2×HCID 8857Ethyl AcetateHCID 513473574-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]piperazin-2-one

Produkt 1

HCID 513567684-[4-(4-Ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]-1-(morpholinomethyl)piperazin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 22242641Methanol--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

Formaldehyde (37% in water, 30 μL, 0.32 mmol) and morpholine (28 μL, 0.32 mmol) were successively added to a solution of 4-[4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluorobenzoyl]-piperazin-2-one (which may be prepared in accordance with the experimental described in Example 7, step 1; 100 mg, 0.26 mmol) in a mixture of methanol/H2O (0.8 mL/0.8 mL). The mixture was stirred at 40° C. for 2 hours prior to the addition of more formaldehyde (37% in water, 30 μL, 0.4 mmol) and more morpholine (32 μL, 0.4 mmol). The reaction mixture was then stirred at 40° C. for two days. The reaction mixture was diluted by addition of ethyl acetate (20 mL) and water (20 mL). After separation, the aqueous layer was extracted with ethyl acetate (2×20 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated under vacuum. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2 to 96:4) as eluent. The title product was obtained as a white solid (55 mg, 44%).

Aufarbeitung

  1. custommay be prepared in accordance with the
  2. stirringThe reaction mixture was then stirred at 40° C. for two days
  3. customAfter separation
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×20 mL)
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by chromatography on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-5886406feca3466a9da4fea1d71a6621
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08623865B2

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