4-[(Methylamino)methyl]piperidine-1-carboxylic acid tert-butyl ester

Chemical Properties

Colorless liquid

Synthesis

General procedure for the synthesis of tert-butyl 4-[(methylamino)methyl]piperidine-1-carboxylate from 1-Boc-4-piperidinyl-N-methylamide: 5.76 g (16.64 mmol) of tert-butyl 4-methylcarbamoyl-piperidine-1-carboxylate was dissolved in 60 mL of anhydrous THF. The solution was slowly added to a 60 mL THF suspension containing 1.4 g (37 mmol) of sodium borohydride at 0 °C and stirred for 30 min. Subsequently, 4.2 g (16.54 mmol) of iodine was added to the 60 mL THF solution. The reaction mixture was heated to reflux and maintained for 18 hours. After completion of the reaction, the mixture was cooled to room temperature and 150 mL of methanol was added slowly and dropwise. The reaction mixture was concentrated and sodium hydroxide solution was added. The reaction mixture was extracted with tert-butyl methyl ether. The organic phases were combined and dried over anhydrous sodium sulfate. A final product of 5 g was obtained in 60% yield of the theoretical value and EI mass spectrum showed m/z = 229 [M + H]+.

References

[1] Patent: WO2008/71646, 2008, A1. Location in patent: Page/Page column 80
[2] Patent: WO2005/7658, 2005, A2. Location in patent: Page 230