Lithium Hexamethyldisilazide → 2,6-Difluoro-N-(1-{[4-[(phenylmethyl)oxy]-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946376Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1946376
[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][NH:9][N:8]=1)=[O:5].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:27]1([CH2:33][O:34][C:35]2[CH:40]=[CH:39][C:38]([CH2:41]Br)=[C:37]([C:43]([F:46])([F:45])[F:44])[CH:36]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[F:1][C:2]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:3]=1[C:4]([NH:6][C:7]1[CH:11]=[CH:10][N:9]([CH2:41][C:38]2[CH:39]=[CH:40][C:35]([O:34][CH2:33][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:36][C:37]=2[C:43]([F:44])([F:45])[F:46])[N:8]=1)=[O:5]

Komponenten

5

Edukt 3

HCID 2733832Lithium HexamethyldisilazideHCID 667703034-(Bromomethyl)-3-(trifluoromethyl)phenyl phenylmethyl etherHCID 178522346HCID 178522346, Verbindung2×

Produkt 1

HCID 469453872,6-Difluoro-N-(1-{[4-[(phenylmethyl)oxy]-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(1.05 g, 4.70 mmol) in anhydrous THF (30 ml) was added 1.0 M lithium bis(trimethylsilyl)amide in THF (4.7 ml, 4.70 mmol) at ambient temperature under nitrogen. The solution was stirred at ambient temperature for 20 min. To the solution was added a solution of 4-(bromomethyl)-3-(trifluoromethyl)phenyl phenylmethyl ether (1.47 g, 4.26 mmol) in THF (15 ml). The mixture was stirred overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (120 ml) and saturated aqueous sodium hydrogen carbonate (100 ml). The phases were separated and the aqueous phase washed with ethyl acetate (30 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave a pale yellow oil (˜2.5 g). The residue was loaded in dichloromethane and purified on silica (100 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.61 g); LCMS: (System 4) MH+=488, tRET=3.37 min.

Aufarbeitung

  1. stirringThe mixture was stirred overnight
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate (120 ml) and saturated aqueous sodium hydrogen carbonate (100 ml)
  4. customThe phases were separated
  5. washthe aqueous phase washed with ethyl acetate (30 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-bb897f3cb9304af09f6c8a6563e8b117
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399436B2

Notizen zur Reaktion

Wird geladen…