Lithium Hexamethyldisilazide → 2-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione

HRID 1946334Notes

Reaction equation

HRID 1946334 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([N:6]2[C:14](=[O:15])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7]2=[O:16])=[N:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:28][C:29]1[CH:34]=[CH:33][C:32]([I:35])=[CH:31][C:30]=1[C:36]([F:39])([F:38])[F:37]>C1COCC1>[I:35][C:32]1[CH:33]=[CH:34][C:29]([CH2:28][N:1]2[CH:5]=[CH:4][C:3]([N:6]3[C:14](=[O:15])[C:13]4[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=4)[C:7]3=[O:16])=[N:2]2)=[C:30]([C:36]([F:37])([F:38])[F:39])[CH:31]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 667721121-(Bromomethyl)-4-iodo-2-(trifluoromethyl)benzeneHCID 178514958HCID 178514958, compound

Product 1

HCID 667708742-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of 2-(1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 28)(0.72 g, 3.38 mmol) in THF (20 ml) was added 1.0 M lithium bis(trimethylsilyl)amide in THF (3.5 ml, 3.50 mmol, Aldrich). The slight suspension was stirred for 30 min. To the yellow solution was added a solution of 1-(bromomethyl)-4-iodo-2-(trifluoromethyl)benzene (for a preparation see within Example 73)(1.24 g, 3.40 mmol) in THF (10 ml). The resulting yellow solution was stirred at ambient temperature under nitrogen overnight. The solvent was removed in vacuo and the residue partitioned between DCM (100 ml) and water (100 ml). To aid the separation, brine (50 ml) and dilute hydrochloric acid (25 ml) were added. The phases were separated and the aqueous phase washed with dichloromethane (50 ml). The organic phases were combined, dried (MgSO4), filtered and the solvent removed in vacuo to leave 2-(1-{[4-iodo-2-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione as an orange solid (1.7 g).

Workup

  1. stirringThe resulting yellow solution was stirred at ambient temperature under nitrogen overnight
  2. customThe solvent was removed in vacuo
  3. customthe residue partitioned between DCM (100 ml) and water (100 ml)
  4. customthe separation, brine (50 ml) and dilute hydrochloric acid (25 ml)
  5. additionwere added
  6. customThe phases were separated
  7. washthe aqueous phase washed with dichloromethane (50 ml)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-a9c8a915c9084f35a198c4a5f8193f9d
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

Loading…