Réaction #49376

Équation de réaction

triphenylphosphine

2-dimethylaminoethanol

DEAD toluene

4-Hydroxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

triphenylphosphine

2-dimethylaminoethanol

DEAD toluene

triphenylphosphine

2-dimethylaminoethanol

DEAD toluene

→

4-[2-(dimethylamino)ethoxy]-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone

Rendement 53.3%

Solvants

THF

water

Conditions de réaction

Traitement

1. 1
   Températurecooling
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
   Extractionextracted with ethyl acetate
6. 6
   LavageThe organic layer was washed with saturated brine
7. 7
   Séchagedried over anhydrous sodium sulfate
8. 8
   AutreThe solvent was evaporated under reduced pressure
9. 9
   Autrethe 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)

Mode opératoire

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%).

Source