Enantioselective synthesis of l-(-)-4-boronophenylalanine...

C - Chemistry – Metallurgy – 07 – F

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C07F 5/02 (2006.01)

Patent

CA 2070202

ABSTRACT OF THE DISCLOSURE A method of making substantially pure L-BPA is disclosed. The method includes the steps of reacting 4- bromobenzaldahyde with ethylene glycol to form 4- bromobenzaldehyds ethylene glycol acetal, sequentially reacting 4-bromobenzaldehyde ethyleneglycol acetal with Mg to produce the Grignard reagent and thereafter reacting with tributyl borate and then converting to an acid environment to form 4-boronobenzaldehyde, reacting 4-boronobenzaldehyde with diethanol amine to form 4-boronobenzaldehyde diethanolamine ester, condensing the 4-boronobenzaldehyde diethanolamine ester with 2-phenyl-2-oxazolin-5-one to form an azlactone, reacting the azlactone with an alkali metal hydroxide to form z-?-benzoylamino-4-boronocinnamic acid, asymmetrically hydrogenating the z- ? -benzoylamino-4- boronocinnamic acid in the presence of a catalyst of a chelate complex of rhodium (I) with chiral bisphosphines to form L-(+)-N-benzoyl-4-boronophenylalanine, and thereafter acidifying the L-(+)-N-benzoyl-4-boronophenylalanine in an organic medium to produce L-BPA.

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