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

HRID 1946376노트

반응식

HRID 1946376 반응식
[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]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 667703034-(Bromomethyl)-3-(trifluoromethyl)phenyl phenylmethyl etherHCID 178522346HCID 178522346, 화합물2회

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-bb897f3cb9304af09f6c8a6563e8b117
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399436B2

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