Reacción #49504

Ecuación de reacción

ammonium fluoride

hydroxymethyltributyltin

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

hydroxymethyltributyltin

→

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

Rendimiento 23.4%

Disolventes

1,4-dioxane

1,4-dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrosynthesized in a similar manner to the method
2. 2
   workup.STIRRINGstirred for 2.3 hours
3. 3
   workup.STIRRINGby stirring for 4 hours
4. 4
   Extracciónextracted with ethyl acetate
5. 5
   LavadoThe organic layer was washed with saturated brine
6. 6
   Secadodried over sodium sulfate
7. 7
   OtroThe solvent was evaporated under reduced pressure
8. 8
   OtroThe residue was purified by preparative thin-layer chromatography (chloroform/methanol=10/1)

Procedimiento

4-Trifluoromethanesulfonyloxy-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (80.0 mg, 0.135 mmol) was dissolved in 1,4-dioxane (2.4 mL), and the solution was added with hydroxymethyltributyltin (87 mg, 0.27 mmol) synthesized in a similar manner to the method described in Synthetic Communications, 1994, vol. 24, p. 1117, and tetrakis(triphenylphosphine)palladium (12.5 mg, 0.0108 mmol), followed by stirring at 90° C. for 2.7 hours under argon atmosphere. The mixture was further added with tetrakis(triphenylphosphine)palladium (6.3 mg, 0.054 mmol) and stirred for 2.3 hours. Further, the mixture was added with hydroxymethyltributyltin (44 mg, 0.14 mmol), tetrakis(triphenylphosphine)palladium (6.3 mg, 0.0054 mmol) and 1,4-dioxane (1.2 mL), followed by stirring for 4 hours. The reaction mixture was added with 10% aqueous ammonium fluoride solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by preparative thin-layer chromatography (chloroform/methanol=10/1) to obtain 4-hydroxymethyl-7-[1-(tert-butoxycarbonyl)-5-(piperidinomethyl)indol-2-yl]isoindolinone (15.0 mg, yield 23%).

Fuente