Dimethylformamide → 4-Chloro-3-hydroxy-7-formyl-2-(1-methyl-1-phenylethyl)isoindolinone

HRID 21116Notes

Reaction equation

HRID 21116 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]([OH:21])[N:5]([C:12]([CH3:20])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:13])[C:6]2=[O:11].CN(CCN(C)C)C.C([Li])(CC)C.CCCCCC.CN([CH:44]=[O:45])C>C1COCC1.O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([CH:44]=[O:45])=[C:7]2[C:3]=1[CH:4]([OH:21])[N:5]([C:12]([CH3:13])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH3:20])[C:6]2=[O:11]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 684900434-Chloro-3-hydroxy-2-(1-methyl-1-phenylethyl)isoindolinoneHCID 178444656HCID 178444656, compound

Product 1

HCID 866282324-Chloro-3-hydroxy-7-formyl-2-(1-methyl-1-phenylethyl)isoindolinoneYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Chloro-3-hydroxy-2-(1-methyl-1-phenylethyl)isoindolinone (1.00 g, 3.31 mmol) was dissolved in THF (40 mL), and the solution was added with TMEDA (1.10 mL, 7.28 mmol), and added with sec-butyllithium-hexane solution (0.99 mol/L, 7.36 mL, 7.28 mmol) by drops at −78° C. for 5 minutes under argon atmosphere, and the mixture was stirred for 2 hours at the same temperature. Then, the mixture was added with DMF (0.384 mL, 4.97 mmol) and warmed from −78° C. to room temperature for 3.5 hours. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography (hexane/ethyl acetate=95/5, 60/40) and preparative thin-layer chromatography (hexane/ethyl acetate=1/1) to obtain 4-chloro-3-hydroxy-7-formyl-2-(1-methyl-1-phenylethyl)isoindolinone (993 mg, yield 91%).

Workup

  1. temperaturewarmed from −78° C. to room temperature for 3.5 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by flash column chromatography (hexane/ethyl acetate=95/5, 60/40)

Sources & evidence

ORD record
ord-a382ecf2fbac4929ad01562428abc71a
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Reaction notes

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