Substituted benzyl ester and its preparation process and novel process for preparing substituted mopipe therefrom

Abstract

The invention discloses a (+)-(3R,4R)-[[2S-[[4-(3-hydroxyphenyl-3,4- dimethyl-1-nipecotic)-methyl]-1-oxo-3-phenylpropyl]amido]benzyl cetate compound and its process for preparing and a new technology for preparation of Mope by the said compound. The new technique of this invention changes the 'one chain' synthesis of the original patent method to the separate 'two chains' preparation, by which the total compound steps are dramatically shortened, the compound cost is reduced to about one-half of the original patent method, and the method is more competitive on the market in price. Furthermore,the reaction condition is moderate, the operating procedure is simple, each reaction step is no need of given condition such as low temperature and absolute water-free, so it is more suitable for industrial production.

Description

technical field

[0001] The present invention relates to the technical field of pharmaceutical chemical synthesis, more specifically (+)-(3R, 4R)-[[2S-[[4-(3-hydroxyphenyl-3,4-dimethyl-1-piper Pyridyl)-methyl]-1-oxo-3-phenylpropyl]amino]acetic acid substituted benzyl ester compound, a preparation method thereof and a new process for preparing avemopi from the compound. Background technique

[0002] Avemopan (alvimopan) is a new type of selective opioid receptor antagonist, mainly used in the treatment of postoperative ileus. The preparation method of this product is currently reported to have two methods, the patented method 1 is based on (+)-3R, 4R-(3-hydroxyphenyl)-3,4-dimethylpiperidine, 2-benzyl ethyl acrylate As the starting material, the target compound is prepared through five steps of addition, hydrolysis, carboxylation, chiral column chromatography, and hydrolysis (see patent CN1065455A); the disadvantage of this method is that the reaction products of each step are...

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