Method for the preparation of...

C - Chemistry – Metallurgy – 07 – C

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C07C 327/32 (2006.01) C07C 51/363 (2006.01) C07D 221/00 (2006.01) C07D 281/00 (2006.01) C07D 513/04 (2006.01)

Patent

CA 2399788

Method for the preparation of (S)-2-acetylthio-3-phenylpropionic acid, wherein (R)-2-bromo-3-phenylpropionic acid is contacted with thioacetic acid and an organic base, for example triethylamine. Preferably the base is metered to a mixture of (R)-2-bromo-3-phenylpropionic acid and thioacetic acid at a temperature between -10 ~C and +30 ~C. (R)-2-bromo-3-phenylpropionic acid is preferably prepared starting from D-phenylalanine, sodium nitrite, HBr and a bromide salt, in an aqueous solution at a temperature between -10 and 30 ~C, and subsequently without isolation converted into (S)-2-acetylthio-3- phenylpropionic acid. The (S)-2-acetylthio-3-phenylpropionic acid obtained can be used in the preparation of pharmaceuticals, in particular ACE inhibitor such as Omapatrilat.

L'invention concerne un procédé de préparation d'acide (S)-2-acétylthio-3-phénylpropionique, dans lequel l'acide (R)-2-bromo-3-phénylpropionique est mis en contact avec un acide thioacétique et une base organique, par exemple la triéthylamine. De préférence, la base est dosée en un mélange d'acide (R)-2-bromo-3-phénylproprionique et d'acide thioacétique à une température comprise entre -10 ·C et +30 ·C. L'acide (R)-2-bromo-3-phénylproprionique est de préférence préparé en partant de D-phénylalanine, de nitrite de sodium, de HBr et d'un sel de bromure, dans une solution aqueuse à une température comprise entre -10 et 30 ·C, et ensuite il est transformé sans isolement en acide (S)-2-acétylthio-3-phénylpropionique. L'acide (S)-2-acétylthio-3-phénylproprionique obtenu peut être utilisé dans la préparation de produits pharmaceutiques, en particulier d'un inhibiteur d'ACE tel que l'Omapatrilat.

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