Lithium Hexamethyldisilazide → HCID 59547919, compound

HRID 1946382Notes

Reaction equation

HRID 1946382 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:39]=[CH:38][C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][C:30]=1[C:40]([F:43])([F:42])[F:41]>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:39]=[CH:38][C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][C:30]=2[C:40]([F:41])([F:43])[F:42])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 23073576Ethyl 4-(bromomethyl)-3-(trifluoromethyl)benzoateHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547919HCID 59547919, 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)(1.29 g, 5.78 mmol) in THF (30 ml) was added 1.0M lithium bis(trimethylsilyl)amide in THF (5.66 ml, 5.66 mmol) at ambient temperature under nitrogen. The solution was stirred at ambient temperature for 30 min. To the solution was added a solution of ethyl 4-(bromomethyl)-3-(trifluoromethyl)benzoate (for a preparation see Intermediate 20)(1.6 g, 5.14 mmol) in THF (20 ml). The mixture was stirred for 3.5 h at ambient temperature under nitrogen. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (75 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 pale yellow oil (2.8 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 (1.68 g); LCMS: (System 4) MH+=454, tRET=3.15 min.

Workup

  1. stirringThe mixture was stirred for 3.5 h at ambient temperature under nitrogen
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between ethyl acetate (100 ml) and saturated aqueous sodium hydrogen carbonate (75 ml)
  4. customThe phases were separated
  5. washthe aqueous phase washed with ethyl acetate (25 ml)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-3315938c66344364a2e581cf33678670
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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