SHORT SYNTHESIS OF 4-HYDROXY PYRROLIDINE-2-ONE FROM TETRAMIC ACID

Abstract

4-Hydroxy pyrrolidine-2-one is useful as intermediates for synthesis of antibiotic and antidepressant agents. The starting chemical compounds used in this study can be obtained easily with cheaper option to synthesize the desired compounds. In this research, short synthesis of 4-hydroxy pyrrolidine-2-one was conducted by using N-Boc-alanine and N-Boc-valine as the amino acid to produce tetramic acids. The amino acids were used readily protected by Boc group to prevent the amino acids from reacting with other compounds. Most of the organic synthesis processes require a long time to generate the desired compounds and have long route of synthesis. This synthesis was done through three steps of reactions. The first reaction is the synthesis of pyrrolidine-2,4-diones from N-Boc-amino acids by Meldrum’s acid mediated reaction and tetramic acid cyclization. EDC.HCl was employed as a carboxyl activating agent in this reaction since it is cheaper and easily obtained. In this reaction, two derivatives of tetramic acids 39 and 40 were successfully synthesized with the yields of 22% and 10% respectively. In the second reaction the synthesized tetramic acids were then subjected to regioselective reduction by using sodium borohydride as the reducing agent in methanol to give 57 with 9% yield and 58 with 6% yield. The third reaction is deprotection of Boc group by adding TFA in DCM to free the amine from the Boc group give 72 and 73 in quantitative yield. All synthesized compounds were purified by column chromatography and characterized using the NMR spectroscopy.

Keywords

• pyrrolidine-2
• 4-dione
• tetramic acid
• meldrum’s acid
• sodium borohydride
• nmr spectroscopy