A Practical and Efficient Synthesis of Thalidomide via Na/Liquid NH3 Methodology1

A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected l-glutamic acid diester via Na/liquid (liq.) NH3 (−33 °C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.