1,2-Dimethoxyethane → methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-3-fluoro-2-hydroxy-4-methylbenzoate

HRID 629441

Reaktionsgleichung

Reaktionsgleichung von HRID 629441
[F:1][C:2]1[C:3]([OH:22])=[C:4]([CH:9]=[C:10](B2OC(C)(C)C(C)(C)O2)[C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].Cl[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>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.O>[N:31]1([C:28]2[CH:29]=[CH:30][C:25]([CH2:24][C:10]3[C:11]([CH3:12])=[C:2]([F:1])[C:3]([OH:22])=[C:4]([CH:9]=3)[C:5]([O:7][CH3:8])=[O:6])=[CH:26][CH:27]=2)[CH:35]=[CH:34][CH:33]=[N:32]1

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 71308871-[4-(chloromethyl)phenyl]-1H-pyrazoleHCID 131735372Methyl 3-fluoro-2-hydroxy-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

Produkt 1

HCID 118468110methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-3-fluoro-2-hydroxy-4-methylbenzoateAusbeute 83,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

Tetrakis(triphenylphosphine)palladium(0) (2.52 g) was added to a mixture of methyl 3-fluoro-2-hydroxy-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (13.5 g), 1-(4-(chloromethyl)phenyl)-1H-pyrazole (8.39 g), sodium carbonate (9.23 g), DME (195 mL) and water (65.0 mL) under argon atmosphere, and the mixture was stirred overnight at 80° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was washed with a mixed solvent of diisopropyl ether-ethyl acetate to give a crude product. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol). The obtained crude products are combined, and washed with diisopropyl ether-ethyl acetate to give the title compound (12.4 g).

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe residue was washed with a mixed solvent of diisopropyl ether-ethyl acetate
  6. customto give a crude product
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol)
  9. customThe obtained crude products
  10. washwashed with diisopropyl ether-ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-5e3edaf7ebf442bfa2eb72343ceb757a
Quelldatensatz
uspto-grants-2016_04
Patentnummer
US09315458B2

Verknüpfte Notizen

Wird geladen…