Synthesis
a) Under argon protection, 2-(1H-indol-3-yl)-N-methoxy-N-methylacetamide (3.00 g, 13.75 mmol) was dissolved in anhydrous THF (60 mL) and the solution was cooled to 0 °C. A THF solution of methylmagnesium bromide (27.49 mL, 27.49 mmol) was added slowly and dropwise with continuous stirring. After 2 hours of reaction, the same amount of methylmagnesium bromide solution (27.49 mL, 27.49 mmol) was added again, and a third addition of methylmagnesium bromide solution (27.49 mL, 27.49 mmol) was made after 3 hours. Upon completion of the reaction, the reaction was quenched by the addition of saturated aqueous ammonium chloride solution, followed by the addition of ethyl acetate (EA) for extraction. The organic phase was separated, washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with petroleum ether/ethyl acetate (gradient elution) as eluent to afford the target product indole-3-acetone (2.35 g). The product was analyzed by LC/MS (method LC5): retention time (RT) = 1.56 min; mass-to-charge ratio (m/z) = 174.1 [M + H]+.
References
[1] Chemical Communications, 2018, vol. 54, # 16, p. 2048 - 2051
[2] Patent: EP3318563, 2018, A1. Location in patent: Paragraph 0155
