Preparation method for 1-benzyl-4-piperidinealdehyde

Abstract

The invention discloses a preparation method for 1-benzyl-4-piperidinealdehyde, which comprises the following steps: (1) preparing 4-pyridylaldehyde, ethylene glycol, p-toluenesulfonic acid and methylbenzene in proportion by weight to obtain 4-(1,3-dioxolame-2-radical) pyridine; (2) performing hydrogenation reaction on the 4-(1,3-dioxolame-2-radical) pyridine by adopting a catalyst to obtain 4-(1,3-dioxolame-2-radical) piperidine; (3) performing benzylation on the 4-(1,3-dioxolame-2-radical) pyridine to obtain 1-benzyl-4-(1,3- dioxolame-2-radical) piperidine; and (4) performing hydrolysis on the 1-benzyl-4-(1,3- dioxolame-2-radical) piperidine by using hydrochloric acid to obtain 1-benzyl-4-piperidinealdehyde, wherein the proportion by weight of the 1-benzyl-4-(1,3- dioxolame-2-radical) piperidine to the hydrochloric acid is 1: 5.45. A raw material which is completely different from that of the prior art is adopted by the preparation method for the 1-benzyl-4-piperidinealdehyde, thereby, the production cost is reduced, and the industrial production is easy.

Description

technical field [0001] The invention relates to the technical field of medicines, and relates to a preparation method of donepezil hydrochloride intermediate 1-benzyl-4-piperidinecarbaldehyde. Background technique Donepezil hydrochloride is a cholinesterase inhibitor for the treatment of AD. It can promote the cognitive ability of patients with mild to moderate senile dementia, improve the mental state of patients, and maintain brain function activity. Due to the good clinical effect of the drug in treatment, many countries are actively producing the drug in order to reduce the cost of use for their patients. And the key intermediate 1-benzyl-4-piperidinecarboxaldehyde of this medicine is a kind of product that is easy to pollute the environment, and is difficult for industrialized production. Therefore, those skilled in the art have been studying the preparation method of this intermediate in recent years. In order to solve the shortcomings in the production of this inte...

AI Technical Summary

Problems solved by technology

However, there are still many deficiencies in the disclosed 1-benzyl-4-piperidinecarbaldehyde preparation method: CN102079720A discloses the use of 1-benzyl-4-piperidinemethanol and a dichloromethane solution of TEMPO in sodium periodate And under the auxiliary oxidation of sodium bromide, carry out oxidation preparation 1-benzyl-4-piperidine carboxaldehyde, though this method has some advantages, but, the raw material price of 1-benzyl-4-piperidine carbinol is expensive, causes production High cost, difficult to industrialized mass production

In addition, in the preparation method using ethyl 4-piperidinecarboxylate and benzyl chloride as raw materials publicly reported abroad, the red aluminum used is prone to safety accidents and pollutes the environment. In the preparation of 1-benzyl-4-piperidinecarbaldehyde The reaction temperature in the process needs to be controlled at minus 60-70°C, which brings great difficulty to the operation, and the cost of industrial production is extremely high; in the preparation method using ethyl 4-piperidinecarboxylate and benzyl chloride as starting materials, It is necessary to react with red aluminum under the catalysis of pyrrole to prepare 1-benzyl-4-piperidinecarbaldehyde. This method is very easy to produce impurities and the purity of the product is low.