Lithium Hexamethyldisilazide → HCID 59547898, compound

HRID 1946391Notes

Reaction equation

HRID 1946391 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+].[CH3:27][O:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[C:30]=1[CH2:36]Br>C1COCC1>[Cl:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([O:28][CH3:27])[C:30]=1[CH2:36][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 223274432-(Bromomethyl)-1-chloro-3-methoxybenzeneHCID 178522346HCID 178522346, compound2×

Product 1

HCID 59547898HCID 59547898, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 2,6-difluoro-N-1H-pyrazol-3-ylbenzamide (for a preparation see Intermediate 9)(0.05 g, 0.224 mmol) in dry THF (1.5 ml) under nitrogen was added a 1 M solution of lithium bis(trimethylsilyl)amide in THF (0.224 ml, 0.224 mmol, Aldrich) dropwise, fairly quickly. The solution was stirred for 30 min then a solution of 2-(bromomethyl)-3-chlorophenyl methyl ether (for a preparation see Intermediate 25)(0.053 g, 0.224 mmol) in dry THF (1.5 ml) was added and stirring continued for 90 min then the solution was left to stand overnight. The solvent was removed in vacuo and the residue was partitioned between chloroform and half saturated sodium bicarbonate and the aqueous phase further extracted with chloroform, the chloroform fractions being filtered through a phase separator. The chloroform was removed in vacuo and the residue purified on MDAP (Method B) to give the title compound as a white solid (0.07 g); LCMS: (System 4) MH+=378, tRET=2.77 min.

Workup

  1. additionwas added
  2. stirringstirring
  3. waitcontinued for 90 min
  4. waitthe solution was left
  5. waitto stand overnight
  6. customThe solvent was removed in vacuo
  7. customthe residue was partitioned between chloroform and half saturated sodium bicarbonate
  8. extractionthe aqueous phase further extracted with chloroform
  9. filtrationthe chloroform fractions being filtered through a phase separator
  10. customThe chloroform was removed in vacuo
  11. customthe residue purified on MDAP (Method B)

Sources & evidence

ORD record
ord-5fe5922a151e447b845cdefcdfdcdb14
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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