Synthesis
The general procedure for the synthesis of 2-methylindole-3-ethylamine from 5-chloro-2-pentanone and phenylhydrazine was as follows: phenylhydrazine (19.8 mL, 200 mmol) and anhydrous ethanol (120 mL) were added to a 500 mL three-necked flask, which was heated to 35 °C under N2 protection. Subsequently, a solution of 5-chloro-2-pentanone (210 mmol) in ethanol (25 mL) was added dropwise. After maintaining the reaction temperature at 40 °C with stirring for 30 min, 160 mL of ethanol was added and the reaction was slowly heated to reflux for 4 hours. Upon completion of the reaction, filtration was performed and the solvent was removed by evaporation. Water (50 mL) was added to the residue and the mixture was adjusted to acidity with 2M hydrochloric acid solution. It was extracted with ethyl acetate (50 mL x 2) and the organic phase was discarded. The aqueous phase was adjusted to alkaline with 20% NaOH solution and extracted again with ethyl acetate (50 mL x 2) and the organic phases were combined. The organic phase was washed with water (50 mL×2) and saturated sodium chloride solution (50 mL×2) sequentially, dried over anhydrous sodium sulfate, filtered and concentrated to obtain the red oily product 2-methylindole-3-ethylamine (24.2 g, 70.1% yield).
References
[1] Organic Letters, 2014, vol. 16, # 13, p. 3480 - 3483
[2] Organic Process Research and Development, 2008, vol. 12, # 6, p. 1078 - 1088
[3] Patent: CN108794375, 2018, A. Location in patent: Paragraph 0043-0045
[4] Patent: CN108752255, 2018, A. Location in patent: Paragraph 0027-0029
[5] Journal of Chemical Research, 2018, vol. 42, # 9, p. 471 - 473
