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Preparation method of a-cyclopentyl methyl mandelate

A technology of methyl cyclopentylmandelate and methyl ester, which is applied in the field of preparation of the intermediate a-cyclopentylmandelic acid methyl ester, and can solve problems such as unsafe use, high cost, and low yield of cyclopentadiene , to achieve the effect of convenient operation, simple steps and high safety

Inactive Publication Date: 2012-10-10
BEIJING HEZHONGMING MEDICAL TECH
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Problems solved by technology

[0007] But as the synthetic method of route 1 has following drawback: (1) raw material monomer cyclopentadiene is obtained by the depolymerization of dicyclopentadiene, but because the high easy carbonization of depolymerization temperature makes the productive rate of cyclopentadiene relatively relatively low; (2) solvent toluene must be used in the two steps of the reaction process, and the toxicity of this substance is relatively large and unsafe to use; (3) for the hydrogenation reaction of the second step, the consumption of required catalyst Raney nickel is more, and the cost (4) The operability of the hydrogenation reaction itself is cumbersome and there are certain risks

Method used

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  • Preparation method of a-cyclopentyl methyl mandelate
  • Preparation method of a-cyclopentyl methyl mandelate
  • Preparation method of a-cyclopentyl methyl mandelate

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preparation example Construction

[0026] The method for preparing methyl α-cyclopentylmandelic acid provided by the present invention, such as figure 1 Shown, including:

[0027] (1) Preparation of a-chlorocyclopentane Grignard reagent: magnesium chips and chlorocyclopentane (C 5 H 9 Cl) react in an organic solvent such as anhydrous ether or tetrahydrofuran to generate a-chlorocyclopentane Grignard reagent;

[0028] (2) Preparation of crude a-cyclopentyl mandelic acid methyl ester: firstly, methyl benzoyl formate (C 9 H 8 O 3 ) Dissolve in an organic solvent such as anhydrous ether or tetrahydrofuran to form a methyl benzoyl formate solution, and react the Grignard reagent of a-chlorocyclopentane generated in step (1) with the methyl benzoyl formate solution Generate crude a-cyclopentyl mandelic acid methyl ester (C 14 H 18 O 3 );

[0029] (3) Purification of the crude methyl a-cyclopentylmandelate: the crude methyl a-cyclopentylmandelate obtained in step (2) is hydrolyzed and esterified to obtain pure methyl a-cycl...

Embodiment 1

[0034] Step 1 is the preparation of a-chlorocyclopentane Grignard reagent, specifically:

[0035] Weigh 146g of magnesium scraps and add it to 1000ml of anhydrous ether (which can be replaced by tetrahydrofuran). Under the protection of nitrogen, first add 90g of chlorocyclopentane dropwise, stir to initiate the reaction, and continue to add 600g of chlorine after the initiation is successful. The reaction of cyclopentane to produce a-chlorocyclopentane is a Grignard reagent. After the initiation is successful, the dripping process should keep the reaction liquid slightly boiling, and then stir for 1 hour after the dripping is completed, for use;

[0036] Step 2 is the preparation of crude a-cyclopentyl mandelic acid methyl ester, specifically:

[0037] Dissolve 500g of methyl benzoyl formate in 1200ml of anhydrous ether, dissolve methyl benzoyl formate in ether or tetrahydrofuran to form a solution of methyl benzoyl formate, and replace the a-chloro ring generated in step 1. The Gr...

Embodiment 2

[0043] Step 1 is the preparation of a-chlorocyclopentane Grignard reagent, specifically:

[0044] Weigh 1.5kg of magnesium scraps and add it to 8L of anhydrous ether (which can be replaced by tetrahydrofuran), under the protection of nitrogen, first add 0.9kg of chlorocyclopentane dropwise, let the reaction start under stirring, and continue to add 6.2kg of chlorine after the initiation is successful Substitute cyclopentane, the dropping rate is maintained at a rate that makes the reaction liquid slightly boiling, and after the dropping is completed, stir for another 2 hours for standby.

[0045] Step 2. Step 2 is the preparation of crude a-cyclopentyl mandelic acid methyl ester, specifically:

[0046] Dissolve 5.2 kg of methyl benzoyl formate in 15 L of anhydrous ether to form a solution of methyl benzoyl formate. Add the a-chlorocyclopentane Grignard reagent in the ether solution prepared in step 1 dropwise to the benzene In the methyl acylformate solution, keep the temperature at...

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Abstract

The invention discloses a preparation method of a-cyclopentyl methyl mandelate, comprising the following steps of: (1) Grignard reagent preparation of a-cyclopentyl chloride: performing a reaction between magnesium granules and cyclopentyl chloride in an ether or tetrahydrofuran solvent to generate an a-cyclopentyl chloride Grignard reagent; (2) preparation of an a-cyclopentyl methyl mandelate crude product: firstly dissolving benzoyl methyl formate in the ether or tetrahydrofuran solvent to form a benzoyl methyl formate solution, and performing a reaction between the a-cyclopentyl chloride Grignard reagent generated during the step (1) and the benzoyl methyl formate solution to generate the a-cyclopentyl methyl mandelate crude product; and (3) purification of the a-cyclopentyl methyl mandelate crude product: carrying out hydrolysis and esterification on the a-cyclopentyl methyl mandelate crude product obtained from the step (2) to obtain the pure a-cyclopentyl methyl mandelate. The raw materials of benzoyl methyl formate, magnesium granules and cyclopentyl chloride are all commonly-used reagents, have wide sources and are easy to obtain. In addition, the preparation method has advantages of simple steps for synthesis, low cost, low toxicity, convenient operation and high security.

Description

[Technical Field] [0001] The invention belongs to the field of pharmaceutical intermediates, and in particular relates to a method for preparing methyl α-cyclopentylmandelic acid intermediates of Weichangning and other medicines. [Background technique] [0002] The molecular formula of a-cyclopentyl mandelic acid methyl ester is C 14 H 18 O 3 , The structural formula is as (I), and the English name is methyl 2-cyclopentyl-2-hydroxy-2-phenylacetate. [0003] [0004] α-Cyclopentyl mandelic acid methyl ester is an intermediate of many drugs, such as Weichangning and other drugs, which is of great significance in synthesis. [0005] The method for synthesizing methyl α-cyclopentylmandelic acid worldwide at this stage is shown in Route 1. [0006] [0007] However, the synthetic method of Route 1 has the following disadvantages: (1) The raw material monomer cyclopentadiene is obtained by the depolymerization of dicyclopentadiene, but due to the high depolymerization temperature and easy c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/732C07C67/343C07C67/60
Inventor 图布新
Owner BEIJING HEZHONGMING MEDICAL TECH
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