Reaction #623386

Reaction equation

lithium diisopropylamide

lithium diisopropylamide

3,4,5-trimethoxybenzonitrile

THF

3-methylpyridine

THF

→

yellow crystals

3,4,5trimethoxy-4-(1H-pyrrolo[2,3-b]pyridin-2-yl)phenol

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture is stirred for a further 30 minutes at the temperature
2. 2
   workup.STIRRINGThe mixture is stirred at 0-5° C. for a further 1.5 h
3. 3
   TemperatureThe reaction mixture is subsequently warmed at 80° C. for 2 h
4. 4
   Temperatureto cool to room temperature
5. 5
   workup.ADDITIONthe mixture is poured onto ice
6. 6
   OtherAfter phase separation
7. 7
   Extractionthe mixture is extracted a further three times with 100 ml of dichloromethane each time
8. 8
   Otherthe combined organic phases are dried
9. 9
   Otherthe solvent is removed in vacuo
10. 10
    OtherThe residue is purified by chromatography over a silica-gel column

Procedure

33 ml of lithium diisopropylamide solution (1 M in THF) are initially introduced at 0° C. under nitrogen, and a solution of 3.6 g of 3-methylpyridine 1 in 50 ml of THF is added dropwise with stirring at 0-5° C. The mixture is stirred for a further 30 minutes at the temperature indicated, and a solution of 5 g of 3,4,5-trimethoxybenzonitrile in 50 ml of THF is subsequently added. The mixture is stirred at 0-5° C. for a further 1.5 h, and finally a further 33 ml of lithium diisopropylamide solution are added. The reaction mixture is subsequently warmed at 80° C. for 2 h. For work-up, the batch is allowed to cool to room temperature, and the mixture is poured onto ice. After phase separation, the mixture is extracted a further three times with 100 ml of dichloromethane each time, the combined organic phases are dried, and the solvent is removed in vacuo. The residue is purified by chromatography over a silica-gel column using ethyl acetate, giving 4.3 g of yellow crystals, which exhibit a melting point of 174.0-175.5° C.

Source