Process of separating chiral isomers of chroman compounds and their derivatives and precursors

摘要

The present invention relates to a process of separating chiral isomers of chroman compounds, particularly tocopherols and tocotrienols as well as the esters and intermediates thereof. It has been found that this process allows a separation of the desired isomer with a higher yield and enables the use of the non-desired isomers in a very efficient way. Said process is particularly useful when implemented in an industrial process. Furthermore, it has been found that this process allows using isomer mixtures as they result from traditional industrial synthesis.

主权项

1. A process of separating chiral isomers of formula (I-A) or (I-B) or (I-C): wherein R1, R3 and R4 are independently from each other hydrogen or methyl groups; R2 represents hydrogen or an phenol protection group; R5 represents either a linear or branched completely saturated C6-25-alkyl group or a linear or branched C8-25-alkyl group comprising at least one carbon-carbon double bond; and wherein * represents the chiral centre of the chiral isomer of formula (I-A) or (I-B) or (I-C); the process comprising the steps of: a) providing a mixture of at least two isomers of formula (I-A) or (I-B) or (I-C); b) performing chromatographic separation of the mixture of isomers of formula (I-A) or (I-B) or (I-C) by means of a chiral phase into desired isomer (I) and residual (I′); c) isomerizing the chirality at the centre indicated by * in formula (I-A) or (I-B) or (I-C) of the isomers of the residual (I′) being separated in step b); d) adding the isomerized isomers obtained in step c) to a mixture of at least two isomers of formula (I-A) or (I-B) or (I-C) being object of further separation; and e) collecting the desired isomer (I).