Method for preparing (S)-tetrahydro-1-naphthoic acid through high-efficiency resolution

A technology of tetrahydronaphthoic acid and naphthoic acid, applied in carboxylate preparation, organic chemical methods, chemical instruments and methods, etc., can solve problems such as environmental pollution, waste of resources, increase production costs, etc., and achieve improved resolution yield , reduce pollution and reduce production costs

Inactive Publication Date: 2017-11-24
HANGZHOU XINBOSI BIOMEDICAL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The total yield of this resolution method is low, less than 30%, and the isomer (R)-1,2,3,4-tetrahydro-1-naphthoic acid produced after resolution is regarded as a by-product and discarded , which not only leads to waste of resources, increases production costs, but also causes environmental pollution

Method used

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  • Method for preparing (S)-tetrahydro-1-naphthoic acid through high-efficiency resolution
  • Method for preparing (S)-tetrahydro-1-naphthoic acid through high-efficiency resolution
  • Method for preparing (S)-tetrahydro-1-naphthoic acid through high-efficiency resolution

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Embodiment 1

[0025] Embodiment 1: ( S )-1,2,3,4-tetrahydro-1-naphthoic acid preparation

[0026] (1) Add 4500ml of ethanol and 750ml of water into a 10L three-necked bottle, and add 250g of 1,2,3,4-tetrahydronaphthoic acid and 462g of quinine in batches. Warming to reflux and stirring for 2h. After that, the temperature was lowered to about 0°C and stirred for 12 hours. Filter and collect the filtrate for later use. The filter cake was air-dried in an oven at 60° C. to dryness to obtain 325 g of a white solid, namely compound III.

[0027] (2) Add 1250ml of ethyl acetate to the white solid compound III obtained above, and then add 625ml of 2mol / L hydrochloric acid aqueous solution, stir for 30min, and let stand to separate layers. The upper organic phase was dried by adding 100 g of anhydrous sodium sulfate, then placed in a water bath at 50°C and concentrated to dryness to obtain 110 g of a white powdery solid, namely compound I.

[0028] (3) Put the filtrate collected in the above r...

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Abstract

The invention relates to a preparation method of a palonosetron hydrochloride key intermediate (S)-1,2,3,4-tetrahydro-1-naphthoic acid as shown in a formula (I). The method comprises the following steps of adding a resolution agent for resolution by adopting 1,2,3,4-tetrahydro-naphthalene acid racemate as a raw material to obtain a salt (III) formed by a (S)-1,2,3,4-tetrahydro naphthalene acid and the resolution agent, and a salt (IV) formed by (R)-1,2,3,4-tetrahydro naphthalene acid and the resolution agent; carrying out salt removing on a compound III and a compound IV separately to obtain compounds (I) and (II); and carrying out racemization on the compound (II) under an alkaline condition to obtain a starting material 1,2,3,4-tetrahydro-naphthalene acid racemate and further carrying out resolution according to the steps. Therefore, the overall yield can be greatly improved, the production cost is reduced and environmental protection is facilitated. The preparation technology of the palonosetron hydrochloride key intermediate provided by the invention is different from the prior art, is safe, environmentally friendly, simple in operation and high in yield, and has relatively great practical value. The formula is as shown in the specification.

Description

technical field [0001] The invention relates to the field of medicine preparation, in particular to a key intermediate of palonosetron hydrochloride ( S )-1,2,3,4-tetrahydro-1-naphthoic acid preparation method. Background technique [0002] ( S )-1,2,3,4-tetrahydro-1-naphthoic acid (compound I) is a chiral molecule and is a key intermediate for the preparation of the chiral drug palonosetron hydrochloride. Palonosetron HCl injection is a safe, effective and long-lasting antiemetic for the prevention and treatment of acute or delayed nausea and vomiting caused by chemotherapy. At present, it has been listed in more than ten countries around the world, and the product name is Aloxi. The chemical name of palonosetron hydrochloride is: (3 s )2-[(3 S )-1-azabicyclo(2.2.2)octyl]-2,3,3 s ,4,5,6-Hexahydro-1H-phenylhydrazine[ de ] isoquinolinone hydrochloride, its structural formula is as follows: [0003] [0004] The chemical resolution method is the most important meth...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C51/02C07C61/39C07B57/00
CPCC07B57/00C07B2200/07C07C51/02C07C61/39C07D453/04
Inventor 陈德宝丁建圣江佳佳刘艳华
Owner HANGZHOU XINBOSI BIOMEDICAL CO LTD
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