Check patentability & draft patents in minutes with Patsnap Eureka AI!

Synthesis method of azasetron hydrochloride intermediate methyl 3-amino-5-chloro-2-hydroxybenzoate

A technology of azasetron hydrochloride and methyl nitrobenzoate, which is applied in the field of synthesis of chemical drug intermediates, can solve the problems of inconvenient after-treatment of iron sludge, unqualified residue, incomplete reaction, etc., and achieve the goal of reducing by-products impact, short reaction time, and yield-enhancing effects

Pending Publication Date: 2020-12-11
SHANGHAI SINE WANXIANG PHARMA +1
View PDF9 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The technical problem to be solved by the present invention is: for the incomplete reaction in the above-mentioned prior art, the inconvenience of post-treatment of iron sludge and the iron salts brought into the product, the high level of related substances in the finished product and the defects of unqualified residues, a kind of azahydrochloride hydrochloride is provided. The synthetic method of setron intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of azasetron hydrochloride intermediate methyl 3-amino-5-chloro-2-hydroxybenzoate
  • Synthesis method of azasetron hydrochloride intermediate methyl 3-amino-5-chloro-2-hydroxybenzoate
  • Synthesis method of azasetron hydrochloride intermediate methyl 3-amino-5-chloro-2-hydroxybenzoate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] The preparation of embodiment 1 intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester

[0023] (1) Dissolve 881g of methyl 5-chloro-2-hydroxy-3-nitrobenzoate in 887mL of ethanol, add 4.29kg of stannous chloride hydrate, heat and reflux at 79°C for 2.5 hours under stirring, and take a small amount with a glass rod The reaction liquid drops on the TLC plate, if the spot has no yellow color, it indicates that the reaction is complete;

[0024] (2) After the reaction was complete, the reaction solution was evaporated to nearly dryness by a rotary evaporator, washed three times by adding diethyl ether in batches, and dried under reduced pressure to obtain 734 g of a white solid with a yield of 95.8%.

Embodiment 2

[0025] Preparation of embodiment 2 intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester

[0026] (1) Dissolve 868g of methyl 5-chloro-2-hydroxy-3-nitrobenzoate in 874ml of ethanol, add 4.65kg of stannous chloride hydrate, heat and reflux at 81°C for 1 hour under stirring, take a small amount with a glass rod The reaction liquid drops on the TLC plate, if the spot has no yellow color, it indicates that the reaction is complete;

[0027] (2) After the reaction was complete, the reaction solution was evaporated to nearly dryness with a rotary evaporator, washed with ether in batches for 3 times, and dried under reduced pressure to obtain 728 g of a white solid with a yield of 96.3%.

Embodiment 3

[0028] Preparation of embodiment 3 intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester

[0029] (1) Dissolve 855g of methyl 5-chloro-2-hydroxy-3-nitrobenzoate in 860ml of ethanol, add 5.00kg of stannous chloride hydrate, heat and reflux at 80°C for 2 hours under stirring, and take a small amount with a glass rod The reaction liquid drops on the TLC plate, if the spot has no yellow color, it indicates that the reaction is complete;

[0030] (2) After the reaction was complete, the reaction solution was evaporated to nearly dryness by a rotary evaporator, washed three times by adding diethyl ether in batches, and dried under reduced pressure to obtain 715 g of a white solid with a yield of 96.1%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a synthesis method of azasetron hydrochloride intermediate methyl 3-amino-5-chloro-2-hydroxybenzoate, which comprises the following steps: (1) dissolving methyl 5-chloro-2-hydroxy-3-nitrobenzoate in ethanol, adding stannous chloride hydrate, conducting heating to 78-82 DEG C while stirring, and conducting refluxing for 1-3 hours; and (2) after the reaction is completed, continuously conducting heating to evaporate the reaction solution to be nearly dry, and sequentially conducting washing and drying under reduced pressure to obtain a white solid, thereby obtaining the product. SnCl2.2H2O is adopted as a reducing agent, ethyl alcohol is adopted as a solvent, nitryl is reduced into amino, the problems that in the prior art, iron mud aftertreatment is inconvenient, andiron salt is brought into a product, so that the content of related substances of a finished product is too high, and residues are unqualified are solved, the defect that amination reaction is incomplete is overcome, the influence of by-products is reduced, and the yield of the target intermediate is improved.

Description

technical field [0001] The invention relates to the technical field of synthesis of chemical drug intermediates, in particular to a synthesis method of azasetron hydrochloride intermediate 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester. Background technique [0002] Azasetron hydrochloride, alias N-(1-azabicyclo2,2,2oct-8-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro-2H- 1,4-Benzoxazine-8-carboxamide hydrochloride, a colorless or almost colorless clear aqueous solution, is an anticancer auxiliary drug, molecular formula: Cl 7 h 20 ClN 3 o 3 ·HCI, suitable for nausea and vomiting caused by cytotoxic drugs and nausea and vomiting caused by gynecological and surgical operations. Its main synthetic route is as follows: [0003] [0004] The existing synthetic method of intermediate III 3-amino-5-chloro-2-hydroxybenzoic acid methyl ester is to use ammonium chloride and iron powder as reducing agent, and the nitro base is dissolved in toluene and then added dropwise to the ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07C229/64C07C227/04C07C227/40
CPCC07C227/04C07C227/40C07C229/64
Inventor 张雅文钱磊高静董佳丽姜丽莉郭晶晶王平叶枝红张弛顾煜
Owner SHANGHAI SINE WANXIANG PHARMA
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com