Improved preparation method of mannityl nicotinate

Abstract

The invention discloses a preparation method of mannityl nicotinate, which takes nicotinic acid, thionyl chloride and mannitol as main raw materials and comprises the steps of acylating chlorination, esterification, refining and the like, wherein the two reactions of acylating chlorination and esterification are finished by a 'one-pot method', and an alkaline neutralization method is adopted to sufficiently precipitate the product after the reaction; and in the refining process, a method of acid solution decoloration and alkaline precipitation taking water as a solvent is adopted to replace the existing traditional technology of adopting a large amount of class-two toxic solvent N,N-dimethylformamide to perform decoloration refining. Through the synthesis method disclosed by the invention, the separation and purification of intermediates are not required, and a crude product can be refined directly without drying, so that the operation steps are reduced, the production period is shortened, and the production cost is lowered, thus the method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical compound, in particular to an improved preparation method of mannohexonicotinoid ester. Background technique [0002] Hexaponicotinate is a cardiovascular drug that can dilate blood vessels and lower blood lipids. It is clinically used to treat coronary heart disease, cerebral thrombosis, atherosclerosis, hypertension, and hyperlipidemia. Compared with similar drugs - inositol nicotinate and sorbitan nicotinate, mannohexonicotinate is easier to hydrolyze in the body than the other two, and the drug effect is faster, and it can also relieve the strong expansion of the terminal effect of niacin itself. Side effects such as facial flushing and gastrointestinal discomfort. As the aging phenomenon in the world and China becomes more and more serious, hexonicotinate, as a high-efficiency antihypertensive and blood lipid-lowering drug, belongs to the category of anti-tumor drugs, cardiovascula...

AI Technical Summary

Problems solved by technology

The above-mentioned production process has many operating steps, the separation and purification of the intermediate nicotinyl chloride hydrochloride and the property of mannohexonicotinate being easily soluble in acid all cause unnecessary product loss

In addition, a large amount of N,N-dimethylformamide is used as a solvent in the refining process, and there are the following problems: 1. Hexapanoic acid ester has little solubility in N,N-dimethylformamide, so it must be used to ensure the dissolution A large amount of solvent, at the same time, in order to ensure the refining yield, it must be concentrated under reduced pressure to evaporate most of the solvent

This not only increases the solvent consumption, but also reduces the batch production capacity of the refining equipment; 2. N,N-dimethylformamide is a second-class toxic solvent, which is restricted in the production of raw materials and has a negative effect on the liver function of the operator. 1. Kidney function is more toxic, and because the solvent is used in the refining process, it will inevitably affect the export sales of hexanicotinate; 3. In industrial production, in order to reduce production costs, the N,N-dimethyl Distillation, dehydration and other treatment of the formamide mother liquor, after qualified

This increases the burden on solvent recovery posts