Synthesis of r(+)alpha-lipoic acid

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, in which the molar ratio S(−)α-methylbenzylamine/racemic 6,8-di-halo-octanoic acid is between 0.45 and 0.65;
• 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 reaction 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 selected from the group consisting of quaternary ammonium or phosphonium salts having the following general formula:
• 2
• where:
• A is nitrogen or phosphorus,
• X is selected from the group consisting of Cl, Br, I, HSO4 e H2PO4, and the substituents R1, R2, R3 e R4 are selected from the group consisting of linear or branched alkyl radicals having one to twenty carbon atoms (C1-C20), said substituents being identical or different one from the other, or only one of said substituents is selected from the group consisting of arylalkyl radicals having the following formula —(CH2)nC6H5 in which n=1-16;
• g) hydrolysis of the ester of R(+)α-lipoic acid.