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

HRID 1946395노트

반응식

HRID 1946395 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+].Br[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=1[C:36]([F:39])([F:38])[F:37]>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]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=2[C:36]([F:38])([F:37])[F:39])[N:8]=1)=[O:5]

참가 물질

5

반응물 3

HCID 2733832Lithium HexamethyldisilazideHCID 667721121-(Bromomethyl)-4-iodo-2-(trifluoromethyl)benzeneHCID 178522346HCID 178522346, 화합물2회

생성물 1

HCID 469452002,6-Difluoro-N-(1-{[4-iodo-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-ylbenzamide (for a preparation see Intermediate 9)(2.65 g, 11.9 mmol) in THF (20 ml) was added 1.0 lithium bis(trimethylsilyl)amide in THF (7.3 ml, 7.30 mmol, Aldrich) and stirred for 15 min. To the solution was added a solution of 1-(bromomethyl)-4-iodo-2-(trifluoromethyl)benzene (1.62 g, 4.44 mmol) in THF (10 ml). The resulting orange solution was stirred at ambient temperature under nitrogen overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (200 ml) and saturated aqueous sodium hydrogen carbonate (150 ml). The phases were separated and the aqueous phase washed with ethyl acetate (50 ml). The combined organic phases were dried (MgSO4), filtered and the solvent removed in vacuo. The residue was loaded in dichloromethane and purified on silica 100 g×2 using 0-50% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.3 g). LCMS: (System 4) MH+=508, tRET=3.22 min.

후처리

  1. stirringThe resulting orange solution was stirred at ambient temperature under nitrogen overnight
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate (200 ml) and saturated aqueous sodium hydrogen carbonate (150 ml)
  4. customThe phases were separated
  5. washthe aqueous phase washed with ethyl acetate (50 ml)
  6. dry with materialThe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. custompurified on silica 100 g×2 using 0-50% ethyl acetate-cyclohexane
  10. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-13fbcf54269f45e7acef8ac28077ceeb
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399436B2

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