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Method for purifying and refining dimethoxy taxane compound

A dimethoxytaxane, purification and refining technology, applied in the direction of organic chemistry, can solve the problems of difficult separation of reaction by-products and compounds, and inability to obtain compounds, so as to improve reaction yield and product purity, and facilitate industrialization The effect of simple production and operation

Active Publication Date: 2012-07-25
无锡紫杉药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the applicant found that this preparation method will produce a large amount of reaction by-products, and it is difficult to separate the reaction by-products from compound (1) through conventional column chromatography and medium and high pressure preparation columns, resulting in the inability to obtain higher purity compounds ( 1)

Method used

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  • Method for purifying and refining dimethoxy taxane compound
  • Method for purifying and refining dimethoxy taxane compound
  • Method for purifying and refining dimethoxy taxane compound

Examples

Experimental program
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Effect test

Embodiment 1

[0018] 30.0 grams of the crude product (purity is 73.8%) obtained according to the preparation method of the compound (1) proposed in the patent CN 1179776A was placed on a chromatographic column (20 cm in inner diameter, 80 cm in height) equipped with 1.2 kg of 400-800 mesh silica gel. centimeter), and use a mixed solvent of petroleum ether / ethyl acetate to elute, collect the eluate containing compound (1), and concentrate to dryness at 40°C under reduced pressure (2.7KPa) to obtain 12.0 grams of crude product. The purity was 89.4%.

[0019] Put the above crude product into tetrahydrofuran (120mL), add acetic anhydride (1.2mL), cerium trichloride heptahydrate (0.94g), react at room temperature for 24 hours, pour into ice water (500mL), add ethyl acetate ( 200mL), stirred thoroughly for 30 minutes. The organic phase was separated, washed with saturated brine (1000 mL×3), dried over anhydrous sodium sulfate, and concentrated to dryness at 40° C. under reduced pressure (2.7 KPa...

Embodiment 2

[0022] 30.0 grams of the crude product (purity is 73.8%) obtained according to the preparation method of the compound (1) proposed in the patent CN 1179776A was placed on a chromatographic column (20 cm in inner diameter, 80 cm in height) equipped with 1.2 kg of 400-800 mesh silica gel. centimeter), and use a mixed solvent of petroleum ether / ethyl acetate to elute, collect the eluate containing compound (1), and concentrate to dryness at 40°C under reduced pressure (2.7KPa) to obtain 12.0 grams of crude product. The purity was 89.4%.

[0023] Put the above crude product into dichloromethane (60mL), add pyridine (1.0mL), add 2,2,2-trichloroethoxycarbonyl chloride (0.87mL) dropwise at 0°C, after dropping, react at room temperature for 24 hours , poured into ice water (500 mL), added dichloromethane (400 mL), and stirred thoroughly for 30 minutes. The organic phase was separated, washed with saturated brine (1000 mL×3), dried over anhydrous sodium sulfate, and concentrated to dr...

Embodiment 3

[0026] 30.0 grams of the crude product (purity is 73.8%) obtained according to the preparation method of the compound (1) proposed in the patent CN 1179776A was placed on a chromatographic column (20 cm in inner diameter, 80 cm in height) equipped with 1.2 kg of 400-800 mesh silica gel. centimeter), and use a mixed solvent of petroleum ether / ethyl acetate to elute, collect the eluate containing compound (1), and concentrate to dryness at 40°C under reduced pressure (2.7KPa) to obtain 12.0 grams of crude product. The purity was 89.4%.

[0027] Put the above crude product into dimethylsulfoxide (24.0mL), add acetic anhydride (16.0mL), acetic acid (1.0mL), react at room temperature for 96 hours, pour into ice water (1000mL), add ethyl acetate (800mL ), fully stirred for 30 minutes. The organic phase was separated, washed with saturated aqueous sodium bicarbonate (1000 mL×3), washed with saturated brine (1000 mL×3), dried over anhydrous sodium sulfate, and concentrated to dryness...

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Abstract

The invention relates to a method for purifying and refining a dimethoxy taxane compound, in particular to the method for purifying and refining 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidinyl-5-carboxylic acid-4alpha-acetoxyl-2alpha-benzoyloxy-5beta,20-epoxy-1beta-hydroxy-9-oxo-7beta,10beta-dimethoxy-11-taxadiene-13alpha ester. The method comprises the following steps: carrying out silica-gel column chromatography on a crude product; eluting the crude product by using petroleum ether / ethyl acetate; collecting the eluate; concentrating to obtain an initial product; allowing reaction between a compounding reagent with the initial product; washing; and refining to prepare the required product. The method is simple in operation and easy for industrial production; and byproducts cannot be generated in the reaction process, so that the reaction yield is increased and the product purity is improved.

Description

technical field [0001] The invention relates to a method for purifying and refining dimethoxytaxane compounds, in particular to a 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R, 4S, 5R )-1,3-oxazolidine-5-carboxylic acid 4α-acetoxy-2α-benzoyloxy-5β,20-epoxy-1β-hydroxy-9-oxy-7β,10β-dimethoxy Purification and refining method of base-11-taxene-13α ester. Background technique [0002] 3-tert-butoxycarbonyl-2-p-methoxyphenyl-4-phenyl-(2R,4S,5R)-1,3-oxazolidine-5-carboxylic acid 4α-acetoxy-2α-benzene Formyloxy-5β, 20-epoxy-1β-hydroxy-9-oxy-7β, 10β-dimethoxy-11-taxene-13α ester, compound (1) is an important taxane compound , It is used in the preparation of various anticancer taxane compounds and raw materials. Patent CN 1179776A discloses a method for preparing the compound. In this method, the dimethyl sulfide intermediate is reacted under the conditions of Raney Ni, hydrogen and ethanol to obtain the crude product of compound (1), which is directly subjected to silica g...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D413/12
Inventor 陈磊郑伟李隆王琼徐信保
Owner 无锡紫杉药业股份有限公司
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