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Cesium carbonate → 4-fluoro-N-{[1-(4-methoxybenzyl)-2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

HRID 1878019
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1878019
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:9](=[O:20])[O:8][C:7]([CH2:25][NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)([C:21]([F:24])([F:23])[F:22])[C:6]=2[CH:36]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[NH:85]1[CH2:89][CH2:88][CH2:87][C:86]1=[O:90]>O1CCOCC1.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:34][C:31]1[CH:32]=[CH:33][C:28]([C:27]([NH:26][CH2:25][C:7]2([C:21]([F:24])([F:23])[F:22])[C:6]3[CH:36]=[C:2]([N:85]4[CH2:89][CH2:88][CH2:87][C:86]4=[O:90])[CH:3]=[CH:4][C:5]=3[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:9](=[O:20])[O:8]2)=[O:35])=[CH:29][CH:30]=1
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Komponenten

8

Edukt 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 44549804N-{[6-bromo-1-(4-methoxybenzyl)-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide

Produkt 1

HCID 68484957
4-fluoro-N-{[1-(4-methoxybenzyl)-2-oxo-6-(2-oxopyrrolidin-1-yl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixed solution of N-{[6-bromo-1-(4-methoxybenzyl)-2-oxo-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-4-yl]methyl}-4-fluorobenzamide (100 mg, 0.176 mmol), tris(dibenzylideneacetone)dipalladium (8.0 mg, 0.008 mmol), xantphos (15.2 mg, 0.024 mmol), cesium carbonate (57.4 mg, 0.176 mmol) and 2-pyrrolidinone (26.8 μL, 0.352 mmol) in dioxane (0.5 mL) was stirred at 120° C. for 30 minutes under microwave irradiation. After the reaction solution was left to cool, the solution was diluted with ethyl acetate and the organic layer was separated. The organic layer was washed with water and saturated brine and then dried over magnesium sulfate. After the drying agent was removed by filtration, the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1), whereby the objective compound (69 mg, 69%) was obtained as a yellow oily substance.

Aufarbeitung

  1. waitAfter the reaction solution was left
  2. temperatureto cool
  3. customthe organic layer was separated
  4. washThe organic layer was washed with water and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. customAfter the drying agent was removed by filtration
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane=1/1), whereby the objective compound (69 mg, 69%)
  9. customwas obtained as a yellow oily substance

Quellen und Nachweise

ORD-Eintrag
ord-c757652dac8d4e8294ce9fc77c09b318
Quelldatensatz
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08314094B2

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