Synthetic method of tapentadol

Abstract

The invention discloses a synthetic method of tapentadol. The method comprises the following steps: reacting meta-substitution cinnamic acid serving as a starting material with a chiral adjuvant to obtain amide; reacting the amide with a nucleophilic reagent and an electrophilic reagent, and introducing two chiral centers to obtain a chiral product; performing reduction and deprotection on the chiral product to obtain chiral alcohol; performing an amination reaction and a substitution reaction on the chiral alcohol to obtain the tapentadol. The tapentadol is synthesized by taking cheap and readily-available (1R,2R)-psedo-ephedrine as the chiral adjuvant, forming two chiral centers by using a one-pot method and performing simper deprotection and subsequent transformation. By adopting the synthetic method, the reaction route can be simplified, post-treatment steps can be reduced, and the production cost is reduced. The synthetic method is more suitable for industrial application.

Description

technical field [0001] The invention relates to a synthesis method of tapentadol, which belongs to the field of drug synthesis. Background technique [0002] Tapentadol, chemical name (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol (English name (-)-( 1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol), is a new type of central analgesic with a dual mechanism of action developed by the German Grünenthal Pharmaceutical Company and Johnson&Johnson Company. On November 21, 2008, it was approved for marketing by the US FDA. Studies have shown that tapentadol has good effects on acute, inflammatory, and chronic neuropathic pain, and can obtain satisfactory blood drug levels through intravenous or oral administration, and is less likely to produce analgesic tolerance and physical dependence than morphine, and compared with Other drugs with equivalent analgesic doses have fewer side effects and have good prospects in the treatment of acute and chronic moderate ...

AI Technical Summary

Problems solved by technology

[0006] However, the above synthetic route uses oxazolidinone as a chiral prosthetic group, which is more expensive, and the second and third step reaction routes are complicated, and there is no one-step ammoniation, and the post-treatment is complicated

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