Lithium Hexamethyldisilazide → HCID 59547920, compound

HRID 1946337Notes

Reaction equation

HRID 1946337 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]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:30]=1[C:38]([F:41])([F:40])[F:39]>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]=[C:33]([N+:35]([O-:37])=[O:36])[CH:32]=[CH:31][C:30]=2[C:38]([F:39])([F:40])[F:41])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 667707571227587-81-6HCID 178522346HCID 178522346, compound

Product 1

HCID 59547920HCID 59547920, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(3.9 g, 17.5 mmol) in THF (35 ml) at ambient temperature was added 1.0 M lithium bis(trimethylsilyl)amide in THF (17.5 ml, 17.50 mmol, Aldrich) dropwise. The solution was stirred for 20 min. To the solution was added a solution of 2-(bromomethyl)-4-nitro-1-(trifluoromethyl)benzene (7.3 g, 25.7 mmol) in THF (10 ml). The resulting dark brown solution was stirred at ambient temperature for 4.5 h. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (125 ml) and saturated aqueous sodium hydrogen carbonate (75 ml). The phases were separated and the organic phase washed with saturated aqueous sodium hydrogen carbonate (25 ml), dried (MgSO4), filtered and the solvent removed in vacuo to leave a brown oil (˜11 g). The residue was loaded in dichloromethane and purified on silica 100 g×2 using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a yellow solid (4.31 g); LCMS: (System 4) MH+=427, tRET=2.80 min.

Workup

  1. customat ambient temperature
  2. stirringThe resulting dark brown solution was stirred at ambient temperature for 4.5 h
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between ethyl acetate (125 ml) and saturated aqueous sodium hydrogen carbonate (75 ml)
  5. customThe phases were separated
  6. washthe organic phase washed with saturated aqueous sodium hydrogen carbonate (25 ml)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-dd846c4863924c18a7a5dd8a1d6ebc6e
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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