Citric Acid → 5-(Aminomethyl)-3-methyl-2-thiophenecarbonitrile

Participants

Reaction Conditions

Reaction Steps

112 ml (179 mmol) of a 1.6 molar solution of n-butyllithium in n-hexane were added in the course of 20 minutes to a solution, cooled to −78° C., of 25.1 ml (179 mmol) of diisopropylamine in 400 ml of tetrahydrofuran. The solution was allowed to reach −35° C. and was cooled again to −78° C., and a solution of 20.0 g (162 mmol) of 2-cyano-3-methylthiophene in 80 ml of tetrahydrofuran was slowly added dropwise at this temperature. The solution acquired a dark red color. Stirring was continued for 45 minutes, 63 ml (811 mmol) of dimethylformamide were slowly added dropwise and stirring was carried out for a further 30 minutes. For working up, a solution of 27 g of citric acid and 160 ml of water was added at −70° C. Evaporating down was carried out in a rotary evaporator, 540 ml of saturated sodium chloride solution were added and extraction was effected with three times 250 ml of diethyl ether. The combined organic extracts were dried over magnesium sulfate. After the drying agent had been filtered off, the solvent was distilled off under reduced pressure from a water jet pump and the residue was purified by column chromatography (mobile phase: 4/1 hexane/ethyl acetate). 23 g (94%) of the title compound were obtained.

Provenance & Evidence