Process for recycling L-cis-lactam as diltiazem intermediate by-product

A technology of l-cis- and diltiazem, applied in organic chemistry and other directions, can solve problems such as route extension and long reaction period

Inactive Publication Date: 2014-04-30
WUHAN INSTITUTE OF TECHNOLOGY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this method, DMSO-Ac 2 O (Albright-Goldman) oxidation method, the reaction period is longer, reaching 24h, and the formation of hydroxymethyl sulfide is an inevitable side reaction of this method, and the reaction must be anhydrous, and in addition, dimethy

Method used

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  • Process for recycling L-cis-lactam as diltiazem intermediate by-product
  • Process for recycling L-cis-lactam as diltiazem intermediate by-product
  • Process for recycling L-cis-lactam as diltiazem intermediate by-product

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Experimental program
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Effect test

Embodiment 1

[0020] Dissolve 5g (0.017mol) of L-cis-lactam (4) in 25ml of DMSO (containing 10% water), then add 5.35g (0.019mol) of IBX, and stir at 80°C for 6h. After the reaction is complete, pour into 200ml of cold water, stir for 1 hour, and then filter to collect the filter cake. The filter cake was washed with ethyl acetate, the mother liquor was washed with water, dried, and concentrated under reduced pressure to obtain 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4-(2H,5H)- Diketone (3), 4.5g, yield 90%, mp161-163°C, e.e.% is 0. The filter cake was dried and recovered to obtain IBA, 4.49g, with a recovery rate of 89%.

Embodiment 2

[0022] Dissolve 5g (0.017mol) of L-cis-lactam (4) in 25ml of DMSO (containing 5% water), then add 9.33g (0.034mol) of IBX, and stir at 5°C for 10h. After the reaction is complete, pour into 200ml of cold water, stir for 1 hour, and then filter to collect the filter cake. The filter cake was washed with ethyl acetate, the mother liquor was washed with water, dried, and concentrated under reduced pressure to obtain 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4-(2H,5H)- Diketone (3), 4.62g, yield 92%, mp162-163°C, e.e.% is 0. The filter cake was dried and recovered to obtain IBA, 7.75g, with a recovery rate of 88%.

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Abstract

The invention relates to a process for recycling L-cis-lactam as a diltiazem intermediate by-product. The process comprises the following steps of: reacting by using L-cis-lactam as a raw material, IBX as an oxidizing agent, and DMSO with the water content of 5-15% as a solvent, performing TLC detection and stopping reaction until the raw material disappears, dissolving in water, stirring for an hour and then performing filtration, collecting filter cakes, washing the filter cakes using ethyl acetate, drying a mother liquor, reducing pressure and concentrating to obtain 2-(4-methoxyphenyl)-1,5-benzothiazepin-3,4(2H,5H)-diketone, drying and recycling the filter cakes, and then obtaining IBA. According to the invention, IBX with high selectivity is used as an oxidizing agent, the reaction condition is moderate, the condition of absolute no water and oxygen is not required, the reaction time is shorter, the post-processing is simple, environmental pollution does not exist, and the reduction product IBA of the IBX can be oxidized as IBX again for recycling use, so that the cost is reduced. Therefore, the method has the characteristics of convenience, high efficiency and economy; the yield of target products can reach more than 90%.

Description

technical field [0001] The invention relates to the recovery of benzothiazepine intermediates, especially the recovery process of L-cis-lactam, a by-product of diltiazem intermediates. Background technique [0002] Diltiazem (Diltiazem, also known as Diltiazem, Tianerxin), the chemical name is cis-(+)-5-[(2-dimethylamino)ethyl]-2-(4-methoxyphenyl) -3-Acetoxy-2,3-dihydro-1,5-phenylpropylthiazepine-4(5H)-one, usually in the form of hydrochloride, belongs to the class of calcium benzothiazepines Antagonist, diltiazem, by acting on the vascular smooth muscle and atrioventricular node of coronary vessels and peripheral vessels, inhibits the influx of calcium ions into cells to display vasodilation and prolong the atrioventricular node conduction time, so it is widely used in coronary arteries. Treatment of heart disease, hypertension, cardiomyopathy and other diseases. [0003] Diltiazem contains a chiral center, and its key intermediate D-cis-3-(4-methoxyphenyl)-3-(2-aminophen...

Claims

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Application Information

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IPC IPC(8): C07D281/02C07D347/00
CPCC07D281/10C07D347/00
Inventor 王凯宋率华喻发全张珩张秀兰刘子维
Owner WUHAN INSTITUTE OF TECHNOLOGY
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