Practical and Scalable Synthesis of Ethyl (R)-Piperidine-3-acetate

Abstract

A practical and scalable synthesis of ethyl (R)-piperidine-3-acetate was achieved from commercially available 3-pyridylacetic acid in 76% overall yield. The practical synthesis was demonstrated on 100-g scale. One-pot reductive N-ethylation of the pyridinium salt with acetonitrile gave an N-ethyl piperidine derivative.

GRAPHICAL ABSTRACT

Keywords:

• Ethyl (R)-piperidine-3-acetate
• hydrogenation
• L-(+)-mandelic acid
• reductive N-ethylation
• resolution

ACKNOWLEDGMENT

Financial support from the Science and Technology Commission of Shanghai Municipality (10XD1401700) is gratefully acknowledged.

Notes

^a The hydrogenation was carried out with 7 (1 g, 3 mmol) in the corresponding solvent (10 mL) at ambient temperature for 8 h in the presence of 5 mol% catalyst.

^b Isolated yield.

^c Methyl piperidine-3-acetate was isolated in 94% yield.