Reaktion #49376

ord-5b2c267b49ba40269cde09b4fcb6f39d

Reaktionsgleichung

c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
CN(C)CCO
2-dimethylaminoethanol
CCOC(=O)/N=N/C(=O)OCC.Cc1ccccc1
DEAD toluene
CC(C)(C)OC(=O)n1c(-c2ccc(O)c3c2C(=O)NC3)cc2cc(CN3CCCCC3)ccc21
4-Hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone
c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
CN(C)CCO
2-dimethylaminoethanol
CCOC(=O)/N=N/C(=O)OCC.Cc1ccccc1
DEAD toluene
c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
CN(C)CCO
2-dimethylaminoethanol
CCOC(=O)/N=N/C(=O)OCC.Cc1ccccc1
DEAD toluene
CN(C)CCOc1ccc(-c2cc3cc(CN4CCCCC4)ccc3n2C(=O)OC(C)(C)C)c2c1CNC2=O
4-[2-(dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone
Ausbeute 53.3%

Lösungsmittel

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Temperaturcooling
  2. 2
    workup.STIRRINGstirred for 14 hours
  3. 3
    workup.STIRRINGstirred for 1.7 hours
  4. 4
    workup.STIRRINGby stirring for 1.3 hours
  5. 5
    Extraktionextracted with ethyl acetate
  6. 6
    WaschenThe organic layer was washed with saturated brine
  7. 7
    Trocknendried over anhydrous sodium sulfate
  8. 8
    SonstigeThe solvent was evaporated under reduced pressure
  9. 9
    Sonstigethe residue was purified by preparative thin-layer chromatography (chloroform/methanol/7 mol/L ammonia-methanol solution=12/0.5/0.5, chloroform/methanol=3/1)

Vorschrift

4-Hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (60.0 mg, 0.130 mmol) was dissolved in THF (3.6 mL), and the solution was added with triphenylphosphine (68 mg, 0.26 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.118 mL) under ice-cooling, followed by stirring for 20 minutes. The reaction mixture was warmed to room temperature and stirred for 14 hours. The mixture was added with triphenylphosphine (68 mg, 0.26 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.118 mL) and stirred for 1.7 hours. Then, the mixture was further added with triphenylphosphine (34 mg, 0.13 mmol), 2-dimethylaminoethanol (0.026 mL, 0.26 mmol) and 40% DEAD-toluene solution (0.059 mL), followed by stirring for 1.3 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 preparative thin-layer chromatography (chloroform/methanol/7 mol/L ammonia-methanol solution=12/0.5/0.5, chloroform/methanol=3/1) to obtain 4-[2-(dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (36.9 mg, yield 53%).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07745641B2uspto-grants-2010_06