Potassium Fluoride → 4-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

HRID 17468

Reaktionsgleichung

Reaktionsgleichung von HRID 17468
Br[C:2]1[C:15]([CH3:16])=[C:14]([C:17]#[N:18])[C:5]2[N:6]=[C:7]([C:9]([N:11]([CH3:13])[CH3:12])=[O:10])[O:8][C:4]=2[C:3]=1[F:19].[C:20](C1(C)C(O)=C(C(C)(C)C)C=CC1)(C)(C)[CH3:21].C(C([Sn])=C(CCCC)CCCC)CCC.[F-].[K+]>O1CCOCC1.O.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(OCC)(=O)C>[C:17]([C:14]1[C:5]2[N:6]=[C:7]([C:9]([N:11]([CH3:13])[CH3:12])=[O:10])[O:8][C:4]=2[C:3]([F:19])=[C:2]([CH:20]=[CH2:21])[C:15]=1[CH3:16])#[N:18]

Komponenten

10

Edukt 4

HCID 522689Potassium FluorideHCID 53438229Tri(butyl)vinyltinHCID 666371922,6-Di-t-butylcresolHCID 685849626-Bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide

Produkt 1

HCID 685862624-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamideAusbeute 62 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

6-Bromo-4-cyano-7-fluoro-N,N,5-trimethyl-1,3-benzoxazole-2-carboxamide (I-127) (500 mg, 1.53 mmol), 2,6-di-tert-butylcresol (3 grains) and tetrakis(triphenylphosphine)palladium(0) (177 mg, 0.15 mmol) were dissolved in 1,4-dioxane (10 ml), then at room temperature, tributylvinyltin (601 μl, 1.99 mmol) was added, followed by stirring under nitrogen atmosphere at 100° C. for 17 hours. After cooling to room temperature, the insoluble matter was separated by filtration with washing with ethyl acetate. The filtrate was washed with saturated brine, then dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the organic layer was washed with water, and dried over anhydrous sodium sulfate. The solvent was evaporated away, the resulting residue was dissolved in tetrahydrofuran (10 ml) and water (5 ml), and at room temperature, potassium fluoride (1.782 g, 30.66 mmol) was added. After vigorously stirring at the same temperature for 23 hours, the reaction liquid was fractionated with ethyl acetate and saturated brine. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, then dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:1) to obtain the entitled compound (261 mg, 62%) as a white solid.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. customthe insoluble matter was separated by filtration
  3. washwith washing with ethyl acetate
  4. washThe filtrate was washed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. washthe organic layer was washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. customThe solvent was evaporated away
  10. dissolutionthe resulting residue was dissolved in tetrahydrofuran (10 ml)
  11. stirringAfter vigorously stirring at the same temperature for 23 hours
  12. customthe reaction liquid
  13. extractionThe aqueous layer was further extracted twice with ethyl acetate
  14. washwashed with saturated brine
  15. dry with materialdried over anhydrous sodium sulfate
  16. customThe insoluble matter was separated by filtration
  17. customthe solvent was evaporated away
  18. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:1)

Quellen und Nachweise

ORD-Eintrag
ord-43a2813d6dcb42548a1e943a0b6a1280
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737166B2

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