Lithium Hexamethyldisilazide → 2,6-difluoro-N-{1-[(2-methyl-5-nitrophenyl)methyl]-1H-pyrazol-3-yl}benzamide

HRID 1946345Notes

Reaction equation

HRID 1946345 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[CH3:38]>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[CH3:38])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 509991612-(Bromomethyl)-1-methyl-4-nitrobenzeneHCID 178522346HCID 178522346, compound

Product 1

HCID 595480222,6-difluoro-N-{1-[(2-methyl-5-nitrophenyl)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) (1.80 g, 8.07 mmol) in THF (30 ml) at ambient temperature under nitrogen was added 1.0 M lithium bis(trimethylsilyl)amide in THF (8 mL, 8.00 mmol) and stirred for 20 min. To the solution was added a solution of 2-(bromomethyl)-1-methyl-4-nitrobenzene (1.81 g, 7.87 mmol) in THF (20 ml) and stirred overnight. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The phases were separated and the aqueous phase washed with ethyl acetate (25 ml). The combined organic extracts were dried (MgSO4), filtered and the solvent removed in vacuo to leave a yellow oil (3.5 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 (2.1 g); LCMS (System 4) MH+=373, tRET=2.60 min.

Workup

  1. customat ambient temperature
  2. stirringstirred overnight
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between ethyl acetate (150 ml) and saturated aqueous sodium hydrogen carbonate (50 ml)
  5. customThe phases were separated
  6. washthe aqueous phase washed with ethyl acetate (25 ml)
  7. dry with materialThe combined organic extracts were dried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-71e5b297790a4d15bfea2391484f6cda
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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