Enantioselective biotransformation for preparation of...

C - Chemistry – Metallurgy – 12 – P

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C12P 7/22 (2006.01) C07C 33/46 (2006.01) C12P 41/00 (2006.01)

Patent

CA 2578298

The invention relates to biocatalytic methods for preparing enantiomerically pure stereoisomers of 1-(2,6-dichloro-3-fluorophenyl)ethanol. Disclosed are methods of preparation of the desired (S)-enantiomer, which methods are based on a combination of enzymatic resolution, chemical esterification and chemical hydrolysis with inversion of 1-(2,6-dichloro-3-fluorophenyl)ethyl esters or stereoselective bio-reduction of 2,6-dichloro-3-fluoro-acetophenone with a biocatalyst such as an enzyme or a microorganism. The chiral (S)-enantiomer can be used in the synthesis of certain enantiomerically enriched, ether linked 2-aminopyridine compounds that potently inhibit auto-phosphorylation of human heptocyte growth factor receptor.

Cette invention concerne des procédés biocatalytiques permettant de préparer des stéréoisomères énantiomériquement purs de 1-(2,6-dichloro-3-fluorophényl)éthanol. Cette invention concerne également des procédés permettant de préparer le (<I>S</I>)-énantiomère souhaité, lesquels procédés consistent à combiner la résolution enzymatique, estérification chimique, et l'hydrolyse chimique avec inversion de 1-(2,6-dichloro-3-fluorophényl)éthyl esters ou bio-réduction stéréosélective de 2,6-dichloro-3-fluoro-acétophénone avec un biocatalyseur, tel qu'un enzyme ou un micro-organisme. Le (<I>S</I>)-énantiomère chiral peut être utilisé dans la synthèse de certains composés enantiomériquement enrichis, à liaison éther 2-aminopyridine inhibant puissamment l'auto-phosphorylation du récepteur du facteur de croissance hépatocyte humain.

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