| Autor: |
Bergeron, Sophie, A. Chaplin, David, H. Edwards, John, S. W. Ellis, Brian, L. Hill, Catherine, Holt-Tiffin, Karen, R. Knight, Jonathan, Mahoney, Thomas, P. Osborne, Andrew, Ruecroft, Graham |
| Zdroj: |
Organic Process Research & Development; May 2006, Vol. 10 Issue: 3 p661-665, 5p |
| Abstrakt: |
An efficient, scaleable synthesis of ethyl (R)-4-cyano-3-hydroxybutyrate, a potential intermediate in the synthesis of Atorvastatin (Lipitor), has been developed. The three-stage process starts with reaction of low-cost epichlorohydrin with cyanide to give 3-hydroxyglutaronitrile (3-HGN). The second stage utilises a nitrilase-catalysed desymmetrisation of 3-HGN. The nitrilase reaction has been optimized to work at 3 M (330 g/L) substrate concentration, pH 7.5, 27 °C. Under these conditions, with an enzyme loading of 6 wt %, 100% conversion and 99% ee product is obtained in 16 h. This material is then esterified to give the target compound, ethyl (R)-4-cyano-3-hydroxybutyrate. The cost-effectiveness of the process is determined by three factors: use of a low-cost starting material, the introduction of the chiral centre by desymmetrisation as opposed to kinetic resolution, and the use of Pfēnex Expression Technology to allow a lower-cost supply of biocatalyst. |
| Databáze: |
Supplemental Index |
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