A kind of resolution method of (r)-1-((2-chlorophenyl)-(phenyl)-methyl)-piperazine

Abstract

The invention belongs to the technical field of chiral drug impurity preparation, and mainly relates to a resolution method of a chiral drug levocetirizine hydrochloride impurity (R)-1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine. The resolution method comprises the steps that racemic 1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine and a resolution agent (S)-(-)-alpha-methylbenzyl isocyanate are dissolved into an organic solvent and react to generate precipitate of (R)-1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine-(S)-(-)-alpha-methylbenzyl isocyanate salt, the precipitate is filtered and washed with acetone to obtain the (R)-1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine-(S)-(-)-alpha-methylbenzyl isocyanate salt, the (R)-1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine-(S)-(-)-alpha-methylbenzyl isocyanate salt is dissolved by adding water, the pH is regulated with a saturated sodium carbonate solution to be 8.0, extraction is conducted by adding ethyl acetate, and drying, filtering and concentrating are conducted to obtain (R)-1-((2-chlorphenyl)-(phenyl)-methyl)-piperazine. The resolution method has the advantages that the product purity is high, the reaction time is short, the reaction temperature is low, and the yield is high; in addition, the solvents are acetone and ethyl acetate and are easy to obtain, free of toxicity, easy to recycle and little in environmental pollution.

Description

technical field

[0001] The invention belongs to the technical field of preparation of chiral drug impurities, and mainly relates to the preparation of chiral drug levocetirizine hydrochloride impurity (R)-1-((2-chlorophenyl)-(phenyl)-methyl)-piperazine Split method. Background technique

[0002] The chiral antihistamine levocetirizine hydrochloride is the (R)-configuration isomer of cetirizine, which has good curative effect in the treatment of histamine-induced allergic rhinitis, allergic erythema, etc., and No central nervous system side effects such as sedation and drowsiness. Therefore, improving the quality of levocetirizine hydrochloride through impurity research has far-reaching significance no matter from the aspect of market prospect or from improving the safety and effectiveness of clinical medication of patients.

[0003] (R)-1-((2-Chlorophenyl)-(phenyl)-methyl)-piperazine is a positioning impurity for preparing levocetirizine hydrochloride liquid-phase importan...

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