A kind of preparation method of ketamine and the synthetic method of intermediate compound

Abstract

The invention discloses an intermediate compound II for synthesizing ketamine. Its chemical structural formula is: the compound II is directly synthesized by one-step reaction of the compound under the action of iodobenzene acetate and azidetrimethylsilane. Compound II synthesizes ketamine through two steps: 1) reduction of azide to amino group; 2) aminomethylation reaction. Compared with the prior art, the HPLC purity of the product of the invention can reach more than 97%. At the same time, the ketamine prepared by the method of the invention has a high degree of industrialization, and the quality of the product is greatly improved compared with the prior art, and there is no intermediate impurity; the process route is simple to operate, low in cost and mild in condition.

Description

A kind of preparation method of ketamine and synthesis method of intermediate compound technical field The invention belongs to the technical field of pharmaceutical synthesis, be specifically related to a kind of intermediate compound of synthesizing ketamine and preparation thereof preparation method. Background technique [0002] Ketamine, chemical name is 2-o-chlorophenyl-2-methylaminocyclohexanone, is a derivative of phenylcyclohexane. in medicine It is generally used as an intravenous general anesthetic in clinical practice; it has bronchiectasis and can be used for the treatment of asthma patients and cerebral blood Tube dilators. The main synthetic method of present ketamine is by the N-methylidene of intermediate 1-hydroxycyclopentyl o-chlorophenyl ketone prepared by rearrangement of amine hydrochloride. However, the rearrangement reaction generally occurs at a high temperature above 160 °C. It also requires microwave radiation, which is not conducive to...

AI Technical Summary

Problems solved by technology

[0009] The oxidizing agent used in this route is easy to open the six-membered ring, and the conditions of the oxidation reaction are harsh, difficult to control, and difficult to operate after treatment; the nitrating reagent used is prone to explosion, and the nitric acid used can cause acute poisoning, shock or renal failure Exhaustion, etc., must be very careful during use, and the waste water produced at the same time is easy to pollute the environment; the reducing agent used is a metal reducing agent such as iron powder. Repeated experiments and researches according to the examples of this patent have found that this type of catalyst is particularly It is easy to be poisoned, the storage time is a little long, the catalytic reaction effect is very poor, the total reaction of nitro group is not complete, even if the reducing agent is added, the reaction cannot be completed completely; and the waste iron powder and acid water produced after the reaction are easy to pollute the environment

Therefore, the route and process conditions are also extremely unsuitable for industrialized production

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