Synthesis method of cyclobenzaprine hydrochloride

Abstract

The invention discloses a synthesis method of cyclobenzaprine hydrochloride, and the method comprises: taking 7-10 ml of redistilled tetrahydrofuran, placing the redistilled tetrahydrofuran into a 100ml three-necked bottle, adding 1-2 pieces of iodine particles, 3-5 drops of 1, 2-dibromoethane and 0.7-1.0 g of zinc powder, slowly heating to a temperature of 35 DEG C, and carrying out a constant temperature reaction for 30-40 min. N, N-dimethyl-3-chloro-zinc propylamine is synthesized from N, N-dimethyl-3-chloropropylamine, iodine, 1,2-dibromoethane and zinc powder in tetrahydrofuran, then cyclobenzaprine is synthesized from the N, N-dimethyl-3-chloro-zinc propylamine and 5 H-dibenzo [a, d] cycloheptatriene-5-one, the cyclobenzaprine hydrochloride is synthesized from the cyclobenzaprine, the quality and purity of the cyclobenzaprine hydrochloride are improved by combination of the cyclobenzaprine and a stirring reaction device, a reaction control technology and a washing purification method. The synthetic reaction process is mild, the safety is high, the product yield is high and the purity of the target product is high. The method is simple and feasible, simple, fast, efficient and energy-saving, and is suitable for industrial mass production.

Description

technical field [0001] The invention relates to the fields of drug synthesis and organic compound synthesis and preparation, in particular to a method for synthesizing cyclobenzaprine hydrochloride. Background technique [0002] Cyclobenzaprine hydrochloride (cyclobenzaprine hydrochloride, 1), chemical name is 5-(3-dimethylaminopropylene) dibenzo [a, d] cycloheptene hydrochloride, it is produced by Merck & Co. The developed muscle relaxants are now on the market in many countries and are clinically used to relieve muscle spasms and the accompanying severe pain in skeletal muscles. It can relieve acute musculoskeletal diseases, sprains and other peripheral injuries, and has great effects on discomfort and pain caused by other connective tissues. This product has fast onset of action, good antispasmodic effect, and little adverse reaction, so it is the first choice drug for treating this kind of pain. [0003] At present, common cyclobenzaprine hydrochloride synthetic method...

AI Technical Summary

Problems solved by technology

However, because the yield of the Wittig reaction is not high, and a strong base sodium amide and a class of organic solvent benzene are used, the risk factor is relatively large, so this route is not suitable for large-scale production

The existing preparation method is relatively simple, but it is difficult to carry out the initiator reaction with ethyl bromide as the Grignard reagent during actual operation, and the follow-up reaction is incomplete, the yield is low, the aftertreatment is loaded down with trivial details, and the product color is too deep and needs recrystallization; 2 ) The dehydration reaction temperature is too high, resulting in a dark product color, and it is unsafe to use ether for extraction; 3) The yield of the salt-forming reaction is low, the product color is very dark and the purity is not high, and post-processing is required

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