N-Methoxy-N,1-diMethylpiperidine-4-carboxaMide

68947-43-3

6638-79-5

215950-19-9

The general procedure for the synthesis of N-methoxy-N,1-dimethylpiperidine-4-carboxamide from 1-methylpiperidine-4-carboxylic acid and N,O-dimethylhydroxylamine hydrochloride was as follows: 1-methylpiperidine-4-carboxylic acid (5.5 g, 38.4 mmol) was dissolved in N,N-dimethylformamide (100 mL) under heating conditions. N,N-diisopropylethylamine (8.0 mL, 46.1 mmol), 1-hydroxybenzotriazole (5.2 g, 38.4 mmol), and N,O-dimethylhydroxylamine hydrochloride (4.1 g, 42.2 mmol) were added sequentially and the reaction mixture was stirred for 5 minutes. Subsequently, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (7.4 g, 38.4 mmol) was added, and the resulting homogeneous solution was stirred at room temperature for 63 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure. The residue was dissolved in water and the pH was adjusted to 9 with 5 N sodium hydroxide solution.The aqueous phase was extracted with dichloromethane, followed by washing with saturated sodium chloride solution and extraction with a solvent mixture of chloroform/isopropanol (3:1). The organic phases were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 9.5 g of yellow liquid product. Purification by fast column chromatography (silica gel as stationary phase, eluent dichloromethane:methanol:ammonium hydroxide=100:10:1) gave 5.7 g (80% yield) of light yellow liquid product. Mass spectrometry (MS) showed m/e: 186 (M+). The results of elemental analysis were consistent with the theoretical value of C9H18N2O2.