Methylamine → 4-(1H-Indol-3-yl)-3-methylamino-butanoic acid ethyl ester

Participants

Reaction Steps

75 ml (680 mmol) of an approximately 30% solution of methylamine in ethanol, 132 g (1.1 mol) of magnesium sulfate monohydrate and 1.5 ml of acetic acid are added to a solution of 33.4 g (136 mmol) of 4-(1H-indol-3-yl)-3-oxo-butanoic acid ethyl ester in 350 ml of methylene chloride. The mixture is stirred at room temperature for 66 hours. The mixture is then filtered and the filter residue is washed with 1.1 liters of methylene chloride. The filtrate is concentrated by evaporation. 250 ml of methanol, 22.33 g (272 mmol) of sodium acetate, 7.8 ml (136 mmol) of acetic acid and 12.08 g (163 mmol, 85% in oil) of sodium cyanoborohydride are added to the residue (a brown oil) and the mixture is stirred at room temperature for 16 hours. The mixture is concentrated by evaporation; 1N hydrochloric acid is added and the mixture is washed twice with diethyl ether. The diethyl ether phases are extracted three times with 1N hydrochloric acid. The combined aqueous phases are cooled and rendered basic with aqueous 50% sodium hydroxide solution. Ethyl acetate is then added. The organic phase is separated off and washed with brine, dried over magnesium sulfate and concentrated by evaporation. The title compound is obtained in the form of a brown oil. 1H-NMR (200 MHz): 8.21 (br. s, 1H), 7.64 (d, 1H), 7.37 (d, 1H), 7.28-7.04 (m, 3H), 4.12 (q, 2H), 3.28 (m, 1H), 2.95 (d, 2H), 2.48 (m, 5H), 1.27 (t, 3H).

Provenance & Evidence