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.) NH 3 (−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.
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Varala et al. (2005) studied this question.
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