Dimethylamine → N,N-dimethylpyrrolidine-3-carboxamide

Participants

Reaction Steps

To a solution of pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester (980 mg, 4.55 mmol) in tetrahydrofuran (20 ml) was added 2,4-dichloro-6-methoxy-[1,3,5]triazine (800 mg, 4.55 mmol) and N-methyl morpholine (1.0 ml, 0.91 mmol). The mixture was stirred at room temperature for 1 hour. Dimethylamine (2.0 M in tetrahydrofuran, 11 ml, 22.0 mmol) was added in one portion. The mixture was stirred at room temperature for an additional 15 hours. Water (2.0 ml) was added, and the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate (20 ml) and 1 N hydrochloric acid (15 ml). The organic layer was washed with a saturated aqueous solution of sodium bicarbonate (10 ml) and brine (10 ml), then dried over sodium sulfate, filtered, and concentrated in vacuo to give the crude product (260 mg, 20%). The crude material was dissolved in dichloromethane (1.0 ml) and trifluoroacetic acid (1.0 ml) was added. The mixture was stirred at room temperature for 90 minutes, and then concentrated in vacuo. The residue was taken into saturated aqueous sodium bicarbonate (10 ml) and extracted three times with chloroform (10 ml). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 180 mg (20% over 2 steps) of pyrrolidine-3-carboxylic acid dimethylamide.

Provenance & Evidence