Splitting method of tetrahydroisoquinoline racemes

Abstract

The invention discloses a new method for resolution of a tetrahydroisoquinoline racemate, consisting of resolving the racemate by a resolving agent with an optical activity (formula II), precipitating diastereomers which S- takes most, getting diastereomer mother liquid which R- takes most, resolving with the resolving agent (formula III or IV) with another optical activity after dissociating themother liquid, getting a single R-stereoisomer. The invention solves the problem of applying single resolving agent and gets the enantiomer with a high yield and a high optical purity and improves the efficiency and benefit, which can be widely used in the racemate resolution field.

Description

technical field [0001] The invention relates to a new method for separating tetrahydroisoquinoline racemate. Background technique [0002] The widely used method to obtain a single enantiomer is the resolution of racemates, especially the formation and separation of diastereoisomers. Although the resolution of many racemates is known, especially the resolving agent is known, usually only one resolving agent is used for crystallization, and then the method that meets the optical purity requirements is obtained by multiple recrystallization methods. single enantiomer. At the same time, some resolving agents are difficult to obtain, and the cost of using a single resolving agent is too high, which is not conducive to industrialization. [0003] Patent US5453510 reports, splits tetrahydropapaverine racemate with N-acetyl-L-leucine, and its process is: first separate S-tetrahydropapaverine with N-acetyl-L-leucine, and then The crude product of R-tetrahydropapaverine was precip...

AI Technical Summary

Problems solved by technology

Although this method uses easily available N-acetyl-L-leucine as a resolving agent, the serious disadvantage is that the required R enantiomer can only be separated from the mother liquor, so that not only the speed of separation is relatively slow, but also the purity Not high, repeated recrystallization is required to obtain the R enantiomer that meets the requirements

[0004] Patent CN200410091127.5 and patent CN96197238.6 respectively report the use of N-acetyl-D-leucine and D-2,4-dichlorophenoxypropionic acid as resolving agents to directly obtain R-tetrahydropapaverine, However, these two resolving agents are difficult to obtain, and the required amount is about the same molar number as the racemate to be resolved, so the amount is large, the cost is high, and industrialization is limited.

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