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

HRID 1946376ノート

反応式

HRID 1946376 の反応式
[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]

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 667703034-(Bromomethyl)-3-(trifluoromethyl)phenyl phenylmethyl etherHCID 178522346HCID 178522346、化合物2 回

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-bb897f3cb9304af09f6c8a6563e8b117
出典データセット
uspto-grants-2013_03
特許番号
US08399436B2

反応ノート

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