Triethylamine → 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole

HRID 1506440Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1506440
[Br:1][C:2]1[CH:10]=[CH:9][C:5](/[CH:6]=[N:7]/[OH:8])=[C:4]([O:11][CH2:12][C:13]#[C:14][C:15]2[C:19]([C:20]([F:23])([F:22])[F:21])=[C:18]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:17][N:16]=2)[CH:3]=1.BrN1C(=O)CCC1=O.C(N(CC)CC)C>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:10]=[CH:9][C:5]2[C:6]3=[N:7][O:8][C:14]([C:15]4[C:19]([C:20]([F:23])([F:21])[F:22])=[C:18]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[O:17][N:16]=4)=[C:13]3[CH2:12][O:11][C:4]=2[CH:3]=1

Komponenten

6

Edukt 3

HCID 8471Triethylamine2×HCID 67184N-bromobutanimide2×HCID 87294070(NE)-N-[[4-bromo-2-[3-[5-phenyl-4-(trifluoromethyl)-1,2-oxazol-3-yl]prop-2-ynoxy]phenyl]methylidene]hydroxylamine

Produkt 1

HCID 671687467-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazoleAusbeute 45 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of (E)-4-bromo-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-ynyloxy)benzaldehyde oxime (Preparation 62E, 0.142 g, 0.305 mmol) in N,N-dimethylformamide (1.5 mL) at 0° C. was added N-bromosuccinimide (0.081 g, 0.458 mmol) followed by triethylamine (0.085 mL, 0.610 mmol). The resulting homogeneous reaction mixture was stirred at 0° C. for 10 min. and then at room temperature for 50 min. HPLC and LCMS analysis indicated that ˜65% of the starting material remained. The reaction mixture was then stirred at 75° C. for 60 min. HPLC analysis indicated that the reaction had progressed to ˜1:1 starting material to product. Additional N-bromosuccinimide (0.081 g, 0.458 mmol) and triethylamine (0.085 mL, 0.610 mmol) were added, and the reaction was heated for an additional 60 min. Very little change was noted upon HPLC analysis. The reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with a 10% aqueous solution of lithium chloride (2×), and washed with brine. The organic layer was collected, and the aqueous layers were sequentially extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated. The solid residue was triturated with methanol with sonication to afford 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole (0.063 g, 0.136 mmol, 45% yield) as a white solid.

Aufarbeitung

  1. waitat room temperature for 50 min
  2. stirringThe reaction mixture was then stirred at 75° C. for 60 min
  3. temperaturethe reaction was heated for an additional 60 min
  4. stirringThe reaction mixture was stirred overnight at room temperature
  5. washwashed with a 10% aqueous solution of lithium chloride (2×)
  6. washwashed with brine
  7. customThe organic layer was collected
  8. extractionthe aqueous layers were sequentially extracted with ethyl acetate
  9. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe solid residue was triturated with methanol with sonication

Quellen und Nachweise

ORD-Eintrag
ord-c01b73c7c5b14b60ba5472f9503400d9
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216972B2

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