Hydrochloric Acid → 2-(1-{[2-(phenyloxy)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione

HRID 1946332Notes

Reaction equation

HRID 1946332 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][CH:32]=[CH:31][C:30]=1[O:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.Cl>C1COCC1.C(Cl)Cl.O.[Cl-].[Na+].O>[C:36]1([O:35][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=2[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)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 2733832Lithium HexamethyldisilazideHCID 226754691-(Bromomethyl)-2-phenoxybenzeneHCID 178514958HCID 178514958, compound

Product 1

HCID 667709652-(1-{[2-(phenyloxy)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 2-(1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 28)(3.08 g, 14.4 mmol) in THF (30 ml) under nitrogen, was treated with 1.0 M lithium bis(trimethylsilyl)amide in THF (15.9 ml, 15.9 mmol, Aldrich) and stirred at room temperature for 15 min. 1-(Bromomethyl)-2-(phenyloxy)benzene (3.8 g, 14.4 mmol, Maybridge) in THF (10 ml) was added and the mixture stirred overnight. The mixture was diluted with DCM (50 ml) and water (50 ml). To the emulsion was added brine (30 ml) and diluted aqueous HCl (15 ml). The resulting phases were separated and the aqueous layer was further extracted with DCM (50 ml). The combined organic extracts were filtered through a hydrophobic frit and the filtrate concentrated under reduced pressure. The residue was loaded in dichloromethane and purified on silica 330 g using 0-50% ethyl acetate-dichloromethane. The appropriate fractions were combined and evaporated in vacuo to give 2-(1-{[2-(phenyloxy)phenyl]methyl}-1H-pyrazol-3-yl)-1H-isoindole-1,3(2H)-dione as an off-white gum (2.35 g).

Workup

  1. stirringthe mixture stirred overnight
  2. customThe resulting phases were separated
  3. extractionthe aqueous layer was further extracted with DCM (50 ml)
  4. filtrationThe combined organic extracts were filtered through a hydrophobic frit
  5. concentrationthe filtrate concentrated under reduced pressure
  6. custompurified on silica 330 g
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-6a97b5af18324a8db02f40a8509a5b1f
Source dataset
uspto-grants-2013_03
Patent number
US08399436B2

Reaction notes

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