Synthesis of r(+)α-lipoic acid

US6864374B2 · kind B2 · utility

Assignee

• LABORATORIO CHIMICO INTERNAZIONALE S.P.A. · IT

Inventors

• Flavio Villani · Parma, IT
• Antonio Nardi · Gambellara, IT
• Annibale Salvi · Milano, IT
• Giovanna Falabella · Milano, IT

Key dates

• Filing date: Oct 8, 2001
• Grant date: Mar 8, 2005
• Expiry date: Mar 25, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D339/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Process for the synthesis of R(+)α-lipoic acid comprising the following stages: a) Salifying of racemic 6,8-halo-octanoic acid with S(−)α-methylbenzylamine; b) separation by filtration of the crystallized diastereoisomeric salt of R(+)6,8-di-halo-octanoic acid-S(−)α-methylbenzylamine; c) purification by re-crystallization of the diastereoisomeric salt of R(+)6,8-di-halo-octanoic acid-S(−)α-methylbenzylamine; (d) separation of the diastereoisomeric salt to obtain R(+)6,8-di-halo-octanoic acid by reation of said salt with strong mineral acids in an aqueous solution with a dilution between 2 and 10% by weight; e) esterification of R(+)6,8-di-halo-octanoic acid to obtain the corresponding alkyl ester; f) reaction of the alkyl ester of R(+)6,8-di-halo-octanoic acid in an organic solvent with an aqueous solution of alkali disulfide in presence of a compound for phase transfer catalysis; g) hydolysis of the ester of R(+)α-lipoic acid.