Dimethylamine → N,N-dimethyl-2-pyrrolidin-3-yl-acetamide

Participants

Reaction Steps

To a solution of 3-dimethylcarbamoylmethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (1.0 g, 4.36 mmol) in tetrahydrofuran (20 ml) was added 2,4-dichloro-6-methoxy-[1,3,5]triazine (765 mg, 4.36 mmol) and N-methyl morpholine (1.44 ml, 13 mmol). The mixture was stirred at room temperature for 1 hour. A dimethylamine solution in tetrahydrofuran (11 ml, 2.0 M, 21.3 mmol) was added in one portion. The mixture was stirred at room temperature for 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 aqueous 1 N hydrochloric acid (15 ml). The organic layer was washed with sodium bicarbonate (sat. 10 ml) and brine (10 mL), then dried over sodium sulfate and evaporated in vacuo to give the crude product (990 mg, 88%). The crude material was dissolved in dichloromethane (2.0 mL) and trifluoroacetic acid (2.0 ml) was added. The mixture was stirred at room temperature for 90 minutes. It Was then concentrated in vacuo and the residue partitioned between saturated aqueous sodium bicarbonate (10 mL) and chloroform. The aqueous layer was extracted three times with chloroform (15 ml) and the combined organic layers were dried over sodium sulfate and concentrated in vacuo to give 530 mg (77% over 2 steps) of N,N-dimethyl-2-pyrrolidin-3-yl-acetamide as a yellowish oil, which was used in the subsequent step without further purification.

Provenance & Evidence