Sodium Carbonate → 1-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanone

HRID 510914Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 510914
Br[C:2]1[C:7]([C:8]2[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=2)=[C:6]([C:16](=[O:18])[CH3:17])[CH:5]=[C:4]([Cl:19])[CH:3]=1.[CH2:20]([O:22][CH:23]([N:25]1[CH:29]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:27]=[N:26]1)[CH3:24])[CH3:21].C(=O)([O-])[O-].[Na+].[Na+].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>[Cl:19][C:4]1[CH:3]=[C:2]([C:28]2[CH:27]=[N:26][N:25]([CH:23]([O:22][CH2:20][CH3:21])[CH3:24])[CH:29]=2)[C:7]([C:8]2[CH:13]=[C:12]([F:14])[CH:11]=[C:10]([F:15])[CH:9]=2)=[C:6]([C:16](=[O:18])[CH3:17])[CH:5]=1

Komponenten

6

Edukt 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 467367981-(1-Ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 679692721-(6-Bromo-4-chloro-3',5'-difluorobiphenyl-2-yl)ethanone

Produkt 1

HCID 679691751-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanoneAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of 1-(6-bromo-4-chloro-3′,5′-difluorobiphenyl-2-yl)ethanone (300 mg, 0.87 mmol), 1-(1-ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (250 mg, 0.96 mmol), and sodium carbonate (280 mg, 2.6 mmol) in 1,4-dioxane (3.0 mL, 38 mmol) was degassed with nitrogen 5 minutes, treated with tetrakis(triphenylphosphine)palladium(0) (100 mg, 0.087 mmol) degassed with additional nitrogen for 5 mins, and heated at 80° C. overnight. The reaction mixture was diluted with water and extracted with ethyl acetate (2×60 mL). The combined organic layers were washed with water and brine, dried with sodium sulfate, filtered, and concentrated to a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (190 mg, 54%).

Aufarbeitung

  1. customdegassed with additional nitrogen for 5 mins
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with ethyl acetate (2×60 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude residue
  8. customPurification via preparative LCMS (XBridge C18 column
  9. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-b397f8f57b6942c8ac9c82f2071339fc
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096600B2

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