Process of lactonization in the preparation of statins
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United States of America Patent
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Jun 29, 1999
Grant Date -
N/A
app pub date -
Apr 22, 1998
filing date -
Oct 28, 1997
priority date (Note) -
Expired
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Abstract
An improved process of lactonization in the preparation of statins (e.g., the HMG--CoA reductase inhibitors lovastatin and simvastatin) employs very mild reaction conditions. The improved process comprises treating the open ring hydroxy acid form of the statins with an excess of acetic acid and in the absence of a strong acid catalyst under mild heating conditions (e.g., ambient to 55.degree. C.), and adding an anti-solvent to the reaction mixture, thereby causing the statins in lactone form to crystalize from the reaction mixture. The acetic acid serves as both a solvent and a catalyst for the lactonization reaction.
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