Roxifiban, dynamic kinetic resolution

Scheme 6.16 Dynamic kinetic resolution of the key intermediate for the synthesis of roxifiban.

Hetero Diels-Alder-Biocatalysis approach for the synthesis of (S)-3- 2-[(methyl-sulfonyl) oxy]ethoxy -4-(triphenylmeth-oxy)-l-butanol methanesulfo-nate successful application of an enzyme resolution process Multi-kilo resolution of XU305, a key intermediate to the platelet glycoprotein Ilb/IIIa receptor antagonist roxifiban via kinetic and dynamic enzymatic resolution... 

Multi-Kilo Resolution of XU305, a Key Intermediate to the Platelet Glycoprotein llb/llla Receptor Antagonist Roxifiban via Kinetic and Dynamic Enzymatic Resolution... 

We describe the process development for the preparation of (R)-XU305, a key intermediate of roxifiban. This process evolved from a small-scale enzymatic kinetic resolution into a pilot plant-scale preparation. The combination of an unusual method of racemization of (S)-XU305 as a thioester permitted a dynamic enzymatic resolution to proceed, removing the need to recycle the less-reactive isomer in order to obtain acceptable overall yields. 

A kinetic resolution of an ester requiring separate steps to recover and recycle the less reactive enantiomer has been transformed into a dynamic resolution of the corresponding thioester. While the thioester route requires an additional synthetic step, the efficiency of this step renders the dynamic resolution route to (R)-l shorter. The development of an alternative route provides our company with additional options for commercial-scale roxifiban preparation. 

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