Hydrochloric Acid → 2-(2-Oxo-2-(pyridin-3-YL)ethyl)isoindoline-1,3-dione

HRID 751660Notes

Reaction equation

HRID 751660 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4].[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K].Cl.CC#N>CN(C=O)C.[Cl-].[Na+].O>[O:4]=[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)[CH2:2][N:15]1[C:11](=[O:21])[C:12]2[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:14]1=[O:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6342AcetonitrileHCID 1514083-(2-Bromoacetyl)pyridineHCID 24194345Phthalimide potassium salt

Product 1

HCID 534035462-(2-Oxo-2-(pyridin-3-YL)ethyl)isoindoline-1,3-dione

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of bromomethylpyridin-3-yl ketone (4.55 g, 16.2 mmol) and potassium phthalimide (6.0 g, 32.4 mmol) in DMF (50 mL) was stirred for 3 days at rt before the added to diluted brine (500 ml, 1:1). The solution was made acidic (pH 2) with diluted hydrochloric acid (1M) before washed with ethyl acetate (2×100 ml). The aqueous layer was then made alkaline (pH 12) again with sodium hydroxide solution (2 M) and extracted with DCM (4×200 ml). The extracts were combined and dried (MgSO4) before concentrated in vacuo. Recrystallisation from methanol (2×) allows to remove crystalline phthalimide and to enrich the title compound in the mother liquer. The crude product was used in Preparation 98 without further purification. δH (d6 DMSO): 5.33 (2H, s), 7.64 (1H, dd), 7.92, 7.97 (4H, 2m), 8.43 (1H, m), 8.88 (1H, m), 9.28 (1H, s); m/z (ES+)=308.13 [M+MeCN +H]+; RT=2.39 min.

Workup

  1. washbefore washed with ethyl acetate (2×100 ml)
  2. extractionextracted with DCM (4×200 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationbefore concentrated in vacuo
  5. customRecrystallisation from methanol (2×)
  6. customto remove crystalline phthalimide
  7. customThe crude product was used in Preparation 98 without further purification

Sources & evidence

ORD record
ord-3dd21b9368864b74b8405282350535d9
Source dataset
uspto-grants-2008_07
Patent number
US07405210B2

Reaction notes

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