An Economically Viable Process for the Synthesis of a Chiral Oxazolidinone ((S)-4-Benzyl-2-oxazolidinone) from Amino Acid

Abstract

An improved and economically affordable synthesis of (S)-4-benzyl-2-oxazolidinone from amino acid has been demonstrated. One pot reaction of phenylalanine with thionyl chloride and sodium borohydride in aqueous methanolic solution yielded phenyl alaninol quantitatively. Success of the reaction depends on the initial formation of smaller particles of the reactants under reaction conditions which became homogenous after some time and finally phenyl alanilol separated out from the solution. The cyclilization of the amino alcohol to oxazolidinone was achieved with diethyl carbonate and potassium carbonate in excellent yield in absence of any solvent. The heterogeneous reaction mixture slowly turned into the desired product during the reaction. Methanol and excess diethyl carbonate were recycled.

Keywords:

• (S)-4-benzyl-2-oxazolidinone
• economical synthesis
• less or no solvent
• phenylalanine
• small particles
• sustainable synthesis

Acknowledgments

P. Munshi and A. Ghosh contributed equally to this manuscript.

A. Ghosh thanks UALR faculty career start up grant and US Department of Energy (Grant number DE-FG36-06GO86072) for financial support. A. Ghosh and P. Munshi also thank Dr. Fumiya Watanabe of UALR Nanotechnology Center for helping to obtain the SEM images.

Notes

^a Reaction carried out in largescale. L-Phenyl alanine 1.1 kg, temp 120°C, time 1 h.