Lithium Hexamethyldisilazide → HCID 59547921, compound

HRID 1946399Notes

Reaction equation

HRID 1946399 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+].BrC[C:29]1[CH:34]=[CH:33][C:32]([O:35][C:36]2[CH:41]=[CH:40][C:39]([CH2:42]Br)=[C:38]([C:44]([F:47])([F:46])[F:45])[CH:37]=2)=[CH:31][C:30]=1C(F)(F)F>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]([CH2:42][C:39]2[CH:40]=[CH:41][C:36]([O:35][C:32]3[CH:33]=[CH:34][CH:29]=[CH:30][CH:31]=3)=[CH:37][C:38]=2[C:44]([F:45])([F:46])[F:47])[N:8]=1)=[O:5]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 86662613HCID 86662613, compoundHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547921HCID 59547921, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(45 mg, 0.20 mmol) in dry THF (3.0 ml) under nitrogen at room temperature was added 1.0 M lithium bis(trimethylsilyl)amide in THF (0.20 ml, 0.20 mmol) dropwise. The solution was stirred for approximately 30 min and then 4-(bromomethyl)-3-(trifluoromethyl)phenyl ether (67 mg, 0.20 mmol) in THF (2 ml) was added. The solution was stirred for 3 h and then left to stand overnight. The solvent was removed under a stream of nitrogen. To the residue was added aqueous sodium bicarbonate and then the residue extracted with chloroform three times. The combined chloroform extracts were filtered through a hydrophobic frit. The filtrate was concentrated in vacuo. The residue was purified on MDAP (Method B). The appropriate fractions were combined and the residue dried under high vacuum to give the title compound as a thick white gum (72.3 mg); LCMS: (System 4) MH+=474, tRET=3.35 min.

Workup

  1. customat room temperature
  2. stirringThe solution was stirred for 3 h
  3. waitleft
  4. waitto stand overnight
  5. customThe solvent was removed under a stream of nitrogen
  6. additionTo the residue was added aqueous sodium bicarbonate
  7. extractionthe residue extracted with chloroform three times
  8. filtrationThe combined chloroform extracts were filtered through a hydrophobic frit
  9. concentrationThe filtrate was concentrated in vacuo
  10. customThe residue was purified on MDAP (Method B)
  11. customthe residue dried under high vacuum

Sources & evidence

ORD record
ord-f60ec60759424a7d9e6b2c74516e55e5
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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