Sodium hydride → 2-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrile

HRID 1875394Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1875394
[H-].[Na+].[CH3:3][C:4]1([CH3:18])[CH2:12][C:11]2[NH:10][N:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[C:7]=2[C:6](=[O:17])[CH2:5]1.[Br:19][C:20]1[CH:27]=[C:26](F)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]>CS(C)=O>[Br:19][C:20]1[CH:27]=[C:26]([N:10]2[C:11]3[CH2:12][C:4]([CH3:18])([CH3:3])[CH2:5][C:6](=[O:17])[C:7]=3[C:8]([C:13]([F:16])([F:15])[F:14])=[N:9]2)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 1189392-Bromo-4-fluorobenzonitrileHCID 441904636,6-Dimethyl-3-(trifluoromethyl)-1,5,6,7-tetrahydro-4H-indazol-4-one

Produkt 1

HCID 118541752-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrileAusbeute 63,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

Sodium hydride (168 mg, 7.02 mmol, 1.0 eq.) was added to a solution of 6,6-dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one (1.63 g, 7.02 mmol, 1.0 eq.) in 35 mL of anhydrous dimethyl sulfoxide. After 15 min 2-bromo-4-fluorobenzonitrile (2.25 g, 11.23 mmol, 1.6 eq.) was added as a solid. The reaction mixture was heated at 45° C. After 23 h the reaction mixture was cooled to ambient temperature and quenched with 10 mL of saturated aqueous ammonium chloride. The mixture was diluted with water and extracted with ethyl acetate (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified on a Biotage (SiO2, hexanes-ethyl acetate) to afford 2-bromo-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.83 g, 63%) as an off-white powder, LC/MS: (M+H)=412.0.

Aufarbeitung

  1. temperatureAfter 23 h the reaction mixture was cooled to ambient temperature
  2. customquenched with 10 mL of saturated aqueous ammonium chloride
  3. additionThe mixture was diluted with water
  4. extractionextracted with ethyl acetate (4×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a Biotage (SiO2, hexanes-ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-46e5244599604f1f81d2134ea86b623d
Quelldatensatz
uspto-grants-2012_11
Patentnummer
US08309548B2

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