Synthesis
GENERAL STEPS: The Vilsmeier-Haack reagent was prepared by slowly adding POCl3 (60 mmol, 6 mL) dropwise to dry DMF (30 mL) pre-cooled to 0 °C under stirring conditions. Subsequently, the reaction mixture was continued to be stirred at 0 °C for 10-15 min. 4-Methylindole (10 mmol) was dissolved in DMF (5 mL) and the resulting solution was added within the Vilsmeier-Haack reagent prepared above. The reaction mixture was warmed to 35 °C with continuous stirring for 1 hour. After completion of the reaction, it was cooled to room temperature and ice water (6 mL) and 30% NaOH aqueous solution (13 mL) were added sequentially, followed by heating the mixture to reflux for 20 min and then cooled to room temperature. The reaction mixture was extracted with dichloromethane (20 mL x 3), the organic phases were combined and dried with anhydrous Na2SO4. The solvent was removed by concentration under reduced pressure and the resulting crude product was purified by fast column chromatography using 15-25% acetone/petroleum ether (boiling range 60-90 °C) as eluent to afford the target product 4-methylindole-3-carbaldehyde.
References
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[2] European Journal of Medicinal Chemistry, 2015, vol. 92, p. 776 - 783
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