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Process for the preparation of benazepril

A molecular formula, the technology of ethyl phenylbutyrate, which is applied in the application field of trifluoromethanesulfonate to prepare the angiotensin-converting enzyme inhibitor benazepril, can solve the problem that the commercial scale has defects and cannot be completely unsatisfactory. Satisfaction, low total yield, etc.

Inactive Publication Date: 2005-02-23
RANBAXY LAB LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the method is still not fully satisfactory and is flawed on a commercial scale due to its low overall yield

Method used

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  • Process for the preparation of benazepril
  • Process for the preparation of benazepril
  • Process for the preparation of benazepril

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preparation of hydrochloric acid (3S)-1-(carboxymethyl-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]2,3,4,5-tetrahydro-1H-[ 1] Benzazepin-2-one

[0032] 5.67 g of ethyl (R)-2-hydroxy-4-phenylbutyrate (99% ee), 2.79 g of pyridine were added to dichloromethane and cooled to -20°C. 10 g of trifluoromethanesulfonic anhydride dissolved in dichloromethane was added over a period of 15 to 20 minutes. Then, the reaction mixture was stirred at -20°C-25°C for 30 minutes and monitored by TLC. After the reaction was completed, the mixture was directly passed through a silica gel column (25 g, 60-125 mesh, 1 inch in diameter) with dichloromethane as the eluent. The fractions were combined and the solvent was removed to give ethyl (R)-2-(trifluoromethanesulfonyloxy)-4-phenylbutanoate (ie, triflate) as an oil. At 30 to 35°C, the oil was dissolved in 15 ml of dichloromethane, and added dropwise to 5.67 g of 1-tert-butoxycarbonylmethyl-3-S-amino-2,3,4,5-tetrahydro- In a mixture fo...

Embodiment 2

[0035] Preparation of hydrochloric acid (3S)-1-(carboxymethyl-[[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-1H- [1] Benzazepin-2-one

[0036] (R)-2-(Trifluoromethanesulfonyloxy)-4-phenylbutanoic acid ethyl ester (ie, trifluoromethanesulfonate) was prepared by the method described in Example 1 to obtain an oil. The oil was dissolved in 15ml of dichloromethane, and 5.67 grams of 1-tert-butoxycarbonylmethyl-3-S-amino-2,3,4,5-tetrahydro-1H-(1)- A solution formed by dissolving benzazepin-2-one and 2.46 g of N-methylmorpholine in dichloromethane. The reaction mixture was stirred for 1 hour and subjected to post-treatment similar to Example 1 to obtain benazepril hydrochloride, 8.20 g, almost white powder, the diastereomer ratio SS:SR=99.35:0.15, yield 91.8%.

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PUM

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Abstract

The present invention relates to an improved process for the preparation of trifluoromethanesulfonic ester of ethyl (R)-2-hydroxy-4-phenylbutyrate, referred to here as triflate in structural Formula I, and to the use of this compound as intermediate for the preparation of ACE (Angiotensin Converting Enzyme) inhibitor, benazepril.

Description

technical field [0001] The present invention relates to the improved preparation method of the trifluoromethanesulfonate of (R)-2-hydroxy-4-phenylbutyric acid ethyl ester, see molecular formula I, hereinafter referred to as trifluoromethanesulfonate (triflate); [0002] [0003] Molecular formula I [0004] It also relates to the application of the compound as an intermediate in the preparation of angiotensin converting enzyme (ACE, Angiotensin Converting Enzyme) inhibitor benazepril (benazepril). Background of the invention [0005] Chemically, benazepril is (3S)-1-(carboxymethyl-[[(1S)-1-ethoxycarbonyl]-3-phenylpropyl]amino)-2,3,4 , 5-tetrahydro-1H-[1]benzazepin-2-one ((3S)-1-(carboxymethyl-[[(1S)-1-(ethoxycarbony)-3-phenylpropyl]amino]-2 , 3,4,5-tetrahydro-1H-[1]benzazepin-2-one). [0006] [0007] Molecular formula II [0008] Benazepril is a well-known long-acting ACE inhibitor, which is mainly used in the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/16A61KA61K31/55C07C303/00C07C303/28C07C307/00C07C309/00C07C309/65C07C311/00C07D223/04C07D487/00C07D491/00C07D498/00C07D513/00
CPCC07D223/16C07C303/28C07C309/65
Inventor R·K·萨普Y·库马S·德D·S·M·库马
Owner RANBAXY LAB LTD
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