Method for preparing moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane

A technology of diazabicyclo and moxifloxacin, which is applied in the field of organic synthesis, can solve the problems of complex reaction, high cost, and increased cost, and achieve the effect of improving product purity and easy operation

Active Publication Date: 2021-06-11
TAIZHOU BIOMEDICAL & CHEM IND RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the routes for industrially synthesizing (S,S)-2,8-diazabicyclo[4,3,0]nonane are basically divided into two categories: (1) reduction of the pyridine ring by palladium carbon, and then by manual The total yield of this route is between 30%~40%, and the yield is relatively low, and the cost is high; (2) by chiral inducing reagents, such as (S)-4-benzene Based on 2-oxazolidinone, asymmetric synthesis is carried out. This route generally has complex reactions, long reaction steps, and high price of chiral inducing reagents, which increases the cost.

Method used

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  • Method for preparing moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane
  • Method for preparing moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane
  • Method for preparing moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane

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Embodiment 1

[0056] Preparation of moxifloxacin intermediate (S,S)-2,8-diazabicyclo[4,3,0]nonane, the method is as follows:

[0057](1) Take 20g of methyl 2-chloromethylnicotinate, dissolve it in 100mL of toluene, replace it with nitrogen three times, then replace it with hydrogen, add a chiral catalyst ([Ir(cod)Cl] 2 R-(+)-BINAP) 0.001g and 1g iodine, and then replace with hydrogen, raise the temperature to 60°C, pressurize to 1.5MPa for hydrogenation reduction, and control the pressure at 0.7-2.0MPa. After the reaction is completed, the resulting hydrogenation reduction reaction is hydraulically filtered into a common reactor, washed twice with saturated aqueous sodium bicarbonate solution, refluxed with water for 1 to 2 hours, and then toluene is recovered. After recovery, (2S,3R)-2- Methyl chloromethylpiperidine-3-carboxylate was dissolved in 100 mL of DMF under nitrogen protection, and was directly used in the next reaction.

[0058] (2) Under the protection of nitrogen, in the DMF s...

Embodiment 2

[0063] Preparation of moxifloxacin intermediate (S,S)-2,8-diazabicyclo[4,3,0]nonane, the method is as follows:

[0064] (1) Take 10g of methyl 2-chloromethylnicotinate, dissolve it in 50mL of xylene, replace it with nitrogen three times, then replace it with hydrogen, add a chiral catalyst ([Ir(cod)Cl] 2 R-(+)-BINAP) 0.001g and 0.3g trichloroisocyanuric acid, and then replace with hydrogen, raise the temperature to 50°C, pressurize to 1.5MPa for hydrogenation reduction, and control the pressure at 0.7-2.0MPa. After the reaction is completed, the resulting hydrogenation reduction reaction is hydraulically filtered into a common reactor, washed twice with saturated aqueous sodium bicarbonate solution, refluxed with water for 1 to 2 hours, and then the xylene is recovered, and the recovery is completed to obtain (2S,3R)-2 -Methyl chloromethylpiperidine-3-carboxylate, under the protection of nitrogen, put 50mL of dioxane into it to dissolve, and directly used in the next reaction....

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Abstract

The invention provides a method for preparing a moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane, and relates to the technical field of organic synthesis. According to the present invention, the 2-chloromethyl methyl nicotinate is subjected to asymmetric hydrogenation catalysis so as to obtain the intermediate with high chiral purity, chiral resolution is not required, and the moxifloxacin intermediate (S, S)-2, 8-diazabicyclo [4, 3, 0] nonane can be obtained through ammonolysis, reduction and cyclization. According to the method provided by the invention, chiral resolution is not needed, the process is simple, the process steps are short, the cost is low, and the product is high in chiral purity and high in total yield.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a method for preparing moxifloxacin intermediate (S,S)-2,8-diazabicyclo[4,3,0]nonane. Background technique [0002] As a new generation of quinolone antibiotics, moxifloxacin has good economic value and broad market prospects. (S,S)-2,8-diazabicyclo[4,3,0]nonane is a synthetic moxifloxacin An important intermediate of cifloxacin. At present, the routes for industrially synthesizing (S,S)-2,8-diazabicyclo[4,3,0]nonane are basically divided into two categories: (1) reduction of the pyridine ring by palladium carbon, and then by manual The total yield of this route is between 30%~40%, and the yield is relatively low, and the cost is high; (2) by chiral inducing reagents, such as (S)-4-benzene Based on 2-oxazolidinone, asymmetric synthesis is carried out. This route generally has complex reactions, long reaction steps, and high price of chiral inducing reagents, which inc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/60C07D211/26C07D471/04
CPCC07D211/60C07D211/26C07D471/04
Inventor 韩得满武承林李运广
Owner TAIZHOU BIOMEDICAL & CHEM IND RES INST CO LTD
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