Dimethylamine → N,N-dimethylpiperidine-3-carboxamide

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Reaction Steps

To a solution of piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (1.0 g, 4.36 mmol) in THF (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 h. A dimethylamine solution in THF (10 mL, 2.0 M, 21.3 mmol) was added in one portion. The mixture was stirred at room temperature for 15 h. Water (2.0 mL) was added and the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate (20 mL) and hydrochloric acid (aqueous 1 N, 15 mL). The organic layer was washed with sodium bicarbonate (sat. 10 mL) and brine (10 mL). It was then dried over sodium sulfate, filtered and concentrated in vacuo to give the crude product (890 mg, 79%). The crude material was dissolved in dichloromethane (3.0 mL) and trifluoroacetic acid (3.0 mL) was added. The mixture was stirred at room temperature for 90 min. It was then concentrated in vacuo. The residue was taken into saturated aqueous sodium bicarbonate (10 mL) and extracted three times with chloroform (15 mL). The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo to give 510 mg (74% over 2 steps) piperidine-3-carboxylic acid dimethylamide, which was used directly in the next step.

Provenance & Evidence