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

HRID 1946395Notes

Reaction equation

HRID 1946395 reaction equation
[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]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 667721121-(Bromomethyl)-4-iodo-2-(trifluoromethyl)benzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 469452002,6-Difluoro-N-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-13fbcf54269f45e7acef8ac28077ceeb
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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