Method for chiral preparation of (S)-tetrahydro-1-naphthoic acid and derivative thereof

A derivative, naphthoic acid technology, applied in the field of pharmaceutical chemical synthesis, can solve the problems of harsh reaction conditions, high safety risks, environmental pollution, etc., and achieve the effect of simple operation and high atom economy

Active Publication Date: 2017-12-01
HANGZHOU XINBOSI BIOMEDICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] Although the yield of this route is higher than that of other process routes (over 80%), it uses a large amount of oxidants, which has high safety risks and causes serious pollution to the environment; at the same time, the raw materials themselves are isomers, and the cost is relatively high. It is also relatively harsh, which is not conducive to industrial amplification

Method used

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  • Method for chiral preparation of (S)-tetrahydro-1-naphthoic acid and derivative thereof
  • Method for chiral preparation of (S)-tetrahydro-1-naphthoic acid and derivative thereof
  • Method for chiral preparation of (S)-tetrahydro-1-naphthoic acid and derivative thereof

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Experimental program
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Effect test

Embodiment 1

[0031] Embodiment 1: ( S )-1,2,3,4-tetrahydro-1-naphthoic acid preparation

[0032] Add 500 ml of toluene and 100 g of 1-naphthoic acid into a 1L three-necked flask, stir and cool down to below 10°C. Add dropwise 84 ml of thionyl chloride and 1 ml N,N -dimethylformamide. Heat up to 40 °C and stir for 4 h. The reaction solution was concentrated to obtain 115 g of yellow oil. Under stirring, add 200 ml of toluene, 115 g of the above-mentioned yellow oil, and 160 ml of triethylamine into a 2 L three-necked flask, and cool to 10°C. drop ( R )-(+)-Ethyl 2-hydroxypropionate toluene solution (68.6 g dissolved in 300 ml toluene), raised to room temperature and stirred for 2 hours. Slowly add 400 ml of 10% citric acid aqueous solution dropwise, and let stand to separate layers. The toluene layer was washed with 100 ml of saturated aqueous sodium chloride solution. The toluene layer was dried over anhydrous sodium sulfate. Filter and wash the filter cake with toluene. The fil...

Embodiment 2

[0035] Embodiment 2: ( S )-1,2,3,4-tetrahydro-6-methoxyl-1-naphthoic acid preparation

[0036] Add 250 ml of toluene and 50 g of 6-methoxy-1-naphthoic acid into a 1L three-necked flask, stir and cool down to below 10°C. Add dropwise 32 ml of thionyl chloride and 1 ml N,N -dimethylformamide. Heat up to 40 °C and stir for 4 h. The reaction solution was concentrated to obtain 54 g of yellow oil. Under stirring, add 100 ml of toluene, 54 g of the above yellow oil, and 80 ml of triethylamine into a 2 L three-necked flask, and cool to 10°C. drop ( R )-(+)-2-Hydroxypropionic acid ethyl ester 29.2 g was dissolved in 150 ml of toluene solution, raised to room temperature and stirred for 2 hours. Slowly add 200 ml of 10% citric acid aqueous solution dropwise, and let stand to separate layers. The toluene layer was washed with 50 ml of saturated aqueous sodium chloride solution. The toluene layer was dried over anhydrous sodium sulfate. Filter and wash the filter cake with tolu...

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Abstract

The invention relates to a method for chiral preparation of (S)-tetrahydro-1-naphthoic acid shown in a formula (V) and a derivative of (S)-tetrahydro-1-naphthoic acid. The method comprises steps as follows: (a) naphthoic acid shown in the formula (I), the derivative of naphthoic acid and (R)-2-hydroxycarboxylate shown in a formula (II) are subjected to an esterification reaction to produce naphthoate shown in a formula (III) and a derivative of naphthoate; (b) naphthoate shown in the formula (III) and the derivative of naphthoate are subjected to a hydrogenation reduction reaction in a proper solvent under the action of a metal catalyst, (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylate shown in a formula (IV) and a derivative of (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylate are obtained; (c) (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylate shown in the formula (IV) and the derivative of (S)-1,2,3,4-tetrahydronaphthalene-1-carboxylate are hydrolyzed under the alkaline condition, and (S)-1,2,3,4-tetrahydro-1-naphthoic acid and the derivative thereof are obtained. The novel method which is different from methods in the prior art is simple to operate, green, environment-friendly, high in atom economy and suitable for industrial production and is used for chiral preparation of (S)-1,2,3,4-tetrahydro-1-naphthoic acid and the derivative thereof.

Description

technical field [0001] The present invention relates to the field of pharmaceutical chemical synthesis, in particular to a ( S A chiral preparation method of )-1,2,3,4-tetrahydro-1-naphthoic acid and derivatives thereof. Background technique [0002] ( S )-1,2,3,4-tetrahydro-1-naphthoic acid is a key intermediate for the synthesis of drug palonosetron hydrochloride, and its structural formula is shown in compound V. [0003] Palonosetron hydrochloride (Palonosetron HCl), developed by Helsinn Company in Switzerland, Palonosetron hydrochloride injection was first launched in the United States in July 2003, the trade name is Aloxi, is a new type of highly selective, high affinity 5 -HT3 receptor inhibitors, the indications are: 1) for the prevention of acute and delayed nausea and vomiting caused by highly and moderately emetogenic chemotherapy in adults; 2) for the prevention of nausea and vomiting in children aged 1 month to under 17 Acute nausea and vomiting caused by eme...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C67/08C07C69/76C07C69/92C07C67/303C07C69/753C07C69/757C07C51/09C07C27/02C07C62/30C07C62/34C07B53/00
CPCC07B53/00C07B2200/07C07C51/09C07C67/08C07C67/303C07C69/76C07C69/92C07C69/753C07C69/757C07C62/30C07C62/34
Inventor 陈德宝丁建圣刘艳华
Owner HANGZHOU XINBOSI BIOMEDICAL CO LTD
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