Preparation method of propranolol hydrochloride single enantiomers

Abstract

The invention relates to a preparation method of propranolol hydrochloride single enantiomers, comprising the following steps of: (1) preparing a saturated solution from a raw material drug of propranolol hydrochloride raceme; (2) injecting the saturated solution to a high efficiency liquid chromatography system, and separating according to conditions that n-hexane-ethanol-isopropanol-diethylamine is used as a mobile phase and a chiral chromatographic column is used as a stationary phase to obtain propranolol enantiomer fraction A and fraction B within different peak value ranges of a chromatogram map; (3) concentrating and then evaporating the propranolol enantiomer fraction A and fraction B respectively to obtain propranolol hydrochloride single enantiomer crude products A and B; (4) adding n-butyl to the propranolol hydrochloride single enantiomer crude products A and B respectively, and dissolving by heating to form hot saturated solutions A and B; and (5) filtering, cooling and drying the hot saturated solutions A and B respectively to obtain propranolol hydrochloride single enantiomers A and B. The preparation method of the invention is simple in process and can simultaneously obtain two enantiomers with high optical rotation purity at a high yield.

Description

technical field

[0001] The invention relates to the field of chiral drug enantiomers, in particular to a preparation method of a single enantiomer of propranolol hydrochloride. Background technique

[0002] Due to the difference in the three-dimensional configuration of the enantiomers of chiral drugs, there are significant differences in the pharmacological activity, metabolic process and toxicity of different enantiomers in the human body. Usually the desired pharmacological activity exists in one enantiomer, while the other enantiomer may have lower activity, or have toxicity or side effects. At present, the US Food and Drug Administration and relevant departments in many western countries have made a decision to prohibit the sale of racemic drugs on the market. It must be split into a single left-handed or right-handed body before it can be marketed as a product. Methods for obtaining optically pure single enantiomers include chiral source synthesis, asymmetric synthesi...