Phthalimide → HCID 21993865, compound

HRID 1978324Notes

Reaction equation

HRID 1978324 reaction equation
[C:1]1(=O)[NH:5][C:4](=O)[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[C:13](=[O:16])([O-])O.[Na+].[C:18]1(=O)[NH:22][C:21](=[O:23])[C:20]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]12.C(O[CH2:33][CH3:34])(=O)C>CN(C)C=O>[C:2]1([CH2:1][CH2:33][CH2:34][N:5]2[CH2:4][C:3]3[C:2](=[CH:10][CH:9]=[C:8]([CH2:18][N:22]4[C:21](=[O:23])[C:20]5=[CH:24][CH:25]=[CH:26][CH:27]=[C:19]5[C:13]4=[O:16])[CH:7]=3)[CH2:1]2)[CH:3]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 6809PhthalimideHCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 24194345Phthalimide potassium salt

Product 1

HCID 21993865HCID 21993865, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 1.835 g (6.863 mM) of 2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-ylmethanol and 1.43 ml (10.3 mM) of triethylamine in 50 ml of tetrahydrofuran was added 0.64 ml (8.24 mM) of methanesulfonyl chloride dropwise with ice-cooling and the mixture was stirred at 0° C. for 0.5 hour. This reaction mixture was poured in aqueous solution of sodium hydrogen carbonate and extracted with 3 portions of diethyl ether. The pooled organic layer was dried over MgSO4 and the solvent was distilled off under reduced pressure. The crude 2-(3-phenylpropan-1-yl)-2,3-dihydro-1H-isoindol-5-ylmethyl methanesulfonate thus obtained was dissolved in 60 ml of N,N-dimethylformamide, followed by addition of 1.40 g (7.55 mM) of potassium phthalimide, and the mixture was stirred at 100° C. for 4 hours. This reaction mixture was poured in aqueous solution of sodium hydrogen carbonate and extracted with 3 portions of ethyl acetate. The pooled organic solution was dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel flash column chromatography (hexane/ethyl acetate=3/1 to 2/1) to provide a mixture of the objective compound and phthalimide. This product was dissolved in ethyl acetate and the solution was washed serially with aqueous solution of sodium hydroxide and saturated aqueous solution of sodium chloride. It was then dried over anhydrous sodium sulfate (Na2SO4) and the solvent was distilled off under reduced pressure to provide the title compound.

Workup

  1. extractionextracted with 3 portions of ethyl acetate
  2. dry with materialThe pooled organic solution was dried over MgSO4
  3. distillationthe solvent was distilled off under reduced pressure
  4. customThe residue was purified by silica gel flash column chromatography (hexane/ethyl acetate=3/1 to 2/1)
  5. customto provide
  6. washthe solution was washed serially with aqueous solution of sodium hydroxide and saturated aqueous solution of sodium chloride
  7. dry with materialIt was then dried over anhydrous sodium sulfate (Na2SO4)
  8. distillationthe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-d705aaaf4b8a486e9ad0e9bf2876910a
Source dataset
uspto-grants-2001_05
Patent number
US06235731B1

Reaction notes

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