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Ammonium Chloride → 2-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile

HRID 17453
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 17453
Br[C:2]1[C:3]([F:17])=[C:4]2[O:8][C:7]([CH:9]3[CH2:11][CH2:10]3)=[N:6][C:5]2=[C:12]([C:15]#[N:16])[C:13]=1[CH3:14].[F:18][C:19]1[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl-].[NH4+]>O1CCOCC1.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>[CH:9]1([C:7]2[O:8][C:4]3[C:5](=[C:12]([C:15]#[N:16])[C:13]([CH3:14])=[C:2]([C:23]4[CH:22]=[CH:21][CH:20]=[C:19]([F:18])[C:24]=4[F:25])[C:3]=3[F:17])[N:6]=2)[CH2:11][CH2:10]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 510414276-Bromo-2-cyclopropyl-7-fluoro-5-methylbenzoxazole-4-carbonitrile

Produkt 1

HCID 685869922-Cyclopropyl-6-(2,3-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrileAusbeute 53 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

6-Bromo-2-cyclopropyl-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-77) (190 mg, 0.64 mmol), 2,3-difluorophenylboronic acid (407 mg, 2.58 mmol) and tripotassium phosphate (274 mg, 1.29 mmol) were dissolved in 1,4-dioxane (6 ml), then at room temperature, tetrakis(triphenylphosphine)palladium(0) (149 mg, 0.13 mmol) was added. The suspension was stirred under nitrogen atmosphere at 95° C. for 86 hours. After cooling to room temperature, the solution was fractionated with ethyl acetate and aqueous saturated ammonium chloride solution. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=9:1) to obtain the entitled compound (111 mg, 53%) as a white solid.

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. extractionThe aqueous layer was extracted twice with ethyl acetate
  3. washwashed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated away
  6. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=9:1)

Quellen und Nachweise

ORD-Eintrag
ord-0103d49164824ac4adb363d831c820eb
Quelldatensatz
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07737166B2

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