Lithium Hexamethyldisilazide → HCID 59547844, compound

HRID 1946357Notes

Reaction equation

HRID 1946357 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+].[C:27]1([CH2:33][O:34][C:35]2[CH:40]=[CH:39][C:38]([Cl:41])=[C:37]([CH2:42]Br)[CH:36]=2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C1COCC1>[Cl:41][C:38]1[CH:39]=[CH:40][C:35]([O:34][CH2:33][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:36][C:37]=1[CH2:42][N:9]1[CH:10]=[CH:11][C:7]([NH:6][C:4](=[O:5])[C:3]2[C:12]([F:16])=[CH:13][CH:14]=[CH:15][C:2]=2[F:1])=[N:8]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 66770954HCID 66770954, compoundHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547844HCID 59547844, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for as preparation see Intermediate 9) (0.790 g, 3.54 mmol) in THF (30 ml) was added 1.0 M lithium bis(trimethylsilyl)amide in THF (3.54 ml, 3.54 mmol). The reaction mixture was stirred for 30 min. To the reaction mixture was added 3-(bromomethyl)-4-chlorophenyl phenylmethyl ether (1.11 g, 3.56 mmol) in THF (10 ml). The reaction was stirred overnight, under nitrogen at ambient temperature. The solvent was evaporated in vacuo. The residue was partitioned between ethyl acetate (100 ml) and water (70 ml). The phases were separated and the organic phase washed with brine (70 ml). The phases were separated and the organic phase was evaporated in vacuo. The sample was loaded in dichloromethane and purified on silica (2×100 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white gum (1.03 g);

Workup

  1. stirringThe reaction was stirred overnight, under nitrogen at ambient temperature
  2. customThe solvent was evaporated in vacuo
  3. customThe residue was partitioned between ethyl acetate (100 ml) and water (70 ml)
  4. customThe phases were separated
  5. washthe organic phase washed with brine (70 ml)
  6. customThe phases were separated
  7. customthe organic phase was evaporated in vacuo
  8. custompurified on silica (2×100 g)
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-9891661b71294277a58dacb1ad32a679
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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