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Preparation method of R-5-(2-Aminopropyl)-2-methoxybenzenesulfonyl with high optically active purity

A technology of methoxybenzenesulfonamide and aminopropyl, which is applied in the field of preparation of optically pure R-5--2-methoxybenzenesulfonamide, which can solve the problem of limiting commercial production advantages, affecting hydrogenation reactions, and being easy to catch fire To achieve the effect of improving the catalyst and operation mode, simple feeding and post-treatment, and mild reaction conditions

Inactive Publication Date: 2007-09-19
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] Patent EP 87306543 discloses the preparation method of chiral R-5-(2-aminopropyl)-2-methoxybenzenesulfonamide, using Raney Ni or PtO 2 As a hydrogenation catalyst, the former Raney Ni is used in a large amount in the reaction, which is 60% of the mass of the raw material, and the properties of Raney Ni affect the hydrogenation reaction, which is inconvenient to store (easy to catch fire when dry), and is not suitable for industrial production operations
PtO 2 As a hydrogenation catalyst, the price is expensive (about 250,000 yuan / kg), and the production cost is high, which limits the commercial production advantages of this product

Method used

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  • Preparation method of R-5-(2-Aminopropyl)-2-methoxybenzenesulfonyl with high optically active purity
  • Preparation method of R-5-(2-Aminopropyl)-2-methoxybenzenesulfonyl with high optically active purity
  • Preparation method of R-5-(2-Aminopropyl)-2-methoxybenzenesulfonyl with high optically active purity

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Experimental program
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Effect test

Embodiment 1

[0032] The first step: 2-methoxy-5-(2-oxopropyl) benzenesulfonamide (24.3g, 100mmol), 12mL phenethylamine, 0.4g 10%Pd / C and 400mL methanol are mixed, in In the autoclave, pass H 2 Replaced three times, then kept the pressure in the kettle at 5 atm, heated to 50°C for 48 hours, stopped the reaction, cooled to room temperature, filtered, concentrated to obtain light yellow viscous oil, added HCl, acidified to pH=4-5, then heated and concentrated A light yellow solid was obtained, which was recrystallized with 400 mL of acetone to obtain a white solid as 5-(2-(1-phenyl-ethylamino)propyl)-2-methoxybenzenesulfonamide hydrochloride, yield 56 %.

[0033] The second step: 3.86g of 5-(2-(1-phenyl-ethylamino)propyl)-2-methoxybenzenesulfonamide hydrochloride (10mmol) and 0.386g 10%Pd / C raw material Mix in the reaction bottle, pass H 2 Replaced three times, then flowed hydrogen under normal pressure, heated to 50 ° C for 24 hours, stopped the reaction, cooled to room temperature, filte...

Embodiment 2

[0035] With reference to Example 1, the difference is that in the first step, the amount of reaction raw material 2-methoxy-5-(2-oxopropyl) benzenesulfonamide is 24.3g, 100mmol, and the amount of α-(+) phenylethylamine 13mL, the amount of catalyst Pd / C is 0.5g, the amount of organic solvent ethanol is 420mL, and the amount of recrystallization solvent acetonitrile is 380mL to obtain 5-(2-(1-phenyl-ethylamino)propyl)-2-methyl Oxybenzenesulfonamide hydrochloride, yield 52%.

[0036] In the second step, 5-(2-(1-phenyl-ethylamino) propyl group)-2-methoxybenzenesulfonamide hydrochloride consumption is 3.86g, and catalyst Pd / C consumption is 0.3g, R- The yield of 5-(2-aminopropyl)-2-methoxybenzenesulfonamide hydrochloride was 94%. The optical purity was determined to be 95% ee.

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Abstract

A producing method for a R-5-(2-aminopropyl)-2-methoxybenzsulfamide is provided, which is including: catalyzed by Pd / C, doing an ammoniation hydrogenation reaction in the organic solvent making use of the chiral phenethylamine and 2-methoxy-5-(2-oxopropyl)benzsulfamide to get a product and acidifying to a hydrochlorate; removing the eshyl phenyl in a condition of hydrogen to get a R-5-(2-aminopropyl)-2-methoxybenzsulfamide hydrochlorate; further reacting with alkali to produce R-5-(2-aminopropyl)-2-methoxybenzsulfamide. The producing method is simple with a good yield and can obtain the product with a high optical purity and can be an industrial production method as the intermediate of the tamsulosin medicine.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and relates to a preparation method of tamsulosin drug raw material R-5-(2-aminopropyl)-2-methoxybenzenesulfonamide with high optical purity. Background technique [0002] Formula (1) R-5-(2-aminopropyl)-2-methoxybenzenesulfonamide is a raw material of tamsulosin medicine. [0003] [0004] Compound 5-[2-[[2-(2-ethoxyphenoxy) ethyl] amino] propyl]-2-methoxybenzenesulfonamide of formula (2), [0005] [0006] It is a commercial drug active substance suitable for the treatment of cardiac insufficiency and benign prostatic hyperplasia. It is disclosed in EP34432 and US 4731478, the molecule is tamsulosin, with an asymmetric carbon (marked with an asterisk in the above formula (2), there are two enantiomers: R or S enantiomer, commercial product The compounded product is the hydrochloride salt of the R(-) enantiomer of tamsulosin, which is levorotatory or (R)(-) tamsulosin hydrochloride. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C311/37C07C303/40C07B53/00
Inventor 陈万里周宏伟刘占祥吴露玲黄宪
Owner ZHEJIANG UNIV
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