Michael P. Burns1, David W. Bauer2, Simon Davidson3, Alastair Denholm3, Aoife Fahy3, Cathal Healy3, John O'Shaughnessy3, Éanna O'Maitiú3, Floriana Stomeo3, Gillian Whittaker3, and John W. Wong1. (1) Pfizer, Groton, CT, (2) Pfizer, Kalamazoo, MI, (3) Pfizer, Cork, Ireland
A process for the biocatalytic reduction of (R)-tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate was developed and implemented at commercial scale. The resulting (3R,5R)-tert-butyl 6-cyano-3,5-dihydroxyhexanoate is a key intermediate in the synthesis of atorvastatin (Lipitor). The benefits of the biocatalytic process include elimination of hazardous and toxic reagents, elimination of cryogenic reaction conditions and multiple distillations, reduction of organic solvent waste, and improved product purity and quality.