Lithium Hexamethyldisilazide → 2,6-Difluoro-N-(1-{[5-(phenyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

HRID 1946402Notes

Reaction equation

HRID 1946402 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]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:32]=[CH:31][C:30]=1[C:42]([F:45])([F:44])[F:43]>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]([O:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:32]=[CH:31][C:30]=2[C:42]([F:43])([F:44])[F:45])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 667707242-(Bromomethyl)-4-(phenyloxy)-1-(trifluoromethyl)benzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 595478692,6-Difluoro-N-(1-{[5-(phenyloxy)-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)benzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(100 mg, 0.448 mmol) in dry THF (6.0 ml) under nitrogen at ambient temperature was added 1.0 M lithium bis(trimethylsilyl)amide (0.45 ml, 0.45 mmol) dropwise and then the solution stirred for approximately 30 min. To the solution was added a solution of crude 2-(bromomethyl)-4-(phenyloxy)-1-(trifluoromethyl)benzene (0.135 g) in dry THF (2.5 ml) and stirred for 7 h. The solvent was removed using a stream of nitrogen. To the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml) and then the residue extracted three times with chloroform. The combined organic extracts were filtered through a hydrophobic frit. The solvent was removed in vacuo and the residue purified on MDAP (Method B). The appropriate fractions were combined and solvent evaporated in vacuo. The residue was dried under high vacuum at 45° C. to give the title compound as a white solid (85 mg); LCMS: (System 4) MH+=474, tRET=3.30 min.

Workup

  1. customat ambient temperature
  2. stirringstirred for 7 h
  3. customThe solvent was removed
  4. additionTo the residue was added saturated aqueous sodium bicarbonate (approximately 7 ml)
  5. extractionthe residue extracted three times with chloroform
  6. filtrationThe combined organic extracts were filtered through a hydrophobic frit
  7. customThe solvent was removed in vacuo
  8. customthe residue purified on MDAP (Method B)
  9. customsolvent evaporated in vacuo
  10. customThe residue was dried under high vacuum at 45° C.

Sources & evidence

ORD record
ord-51eccecd87944105b67db458dbcb9371
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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