Preparation technique for mezlocillin

A preparation technology of mezlocillin acid, which is applied in the field of drug synthesis, can solve problems such as poor quality stability, high solvent residue, and poor crystal form of the product, and achieve good stability, low solvent residue, and good crystal shape.

Active Publication Date: 2009-10-07
SHANDONG RUIYING PIONEER PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] However, the product obtained by this synthetic route has the following disadvantages: the crystal form of the product is ...

Method used

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  • Preparation technique for mezlocillin

Examples

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Effect test

Embodiment 1

[0022] At 20°C, add 100mL of water, 6g of sodium bicarbonate and 40mL of acetone into a 250mL four-neck flask, add 12.5g of ampicillin in sequence while stirring, cool down to 16°C, and slowly add 1-chloroformyl-3- 6.6 g of methylsulfonyl-2-imidazolidinone was added, and the reaction was continued for another 30 minutes. After complete reaction, 60 mL of isopropyl ether was added for extraction, and after separation, the aqueous phase was filtered to a crystallization kettle.

[0023] Add 50mL of methyl acetate, cool down to 20°C and slowly add dilute hydrochloric acid dropwise to carry out acidification and crystallization, adjust the pH to 2.0, and stir for 30 minutes under temperature control. . Vacuum -0.08, 40 ° C under reduced pressure drying for 4 hours to obtain 16.0 g of needle crystals.

[0024] Quality index: content 99.5%, single impurity 0.09%, total impurity 0.25%, solvent residue 0.28%.

Embodiment 2

[0026] At 25°C, add 110mL of water, 6g of sodium bicarbonate and 45mL of acetone into a 250mL four-neck flask, add 12.5g of ampicillin in sequence while stirring, cool down to 17°C, and slowly add 1-chloroformyl-3- 6.5 g of methylsulfonyl-2-imidazolidinone, and the reaction was continued for another 30 minutes. After complete reaction, 50 mL of isopropyl ether was added for extraction, and the aqueous phase was filtered to a crystallization tank after separation.

[0027] Add 55 mL of methyl acetate, cool down to 22°C and slowly add dilute hydrochloric acid dropwise to carry out acidification and crystallization, adjust the pH to 2.2, and stir for 40 minutes under temperature control. . Vacuum -0.09, 35 ° C under reduced pressure drying for 5 hours to obtain 16.3 g of needle crystals.

[0028] Quality index: content 99.56%, single impurity 0.1%, total impurity 0.26%, solvent residue 0.25%.

Embodiment 3

[0030] At 25°C, add 120mL of water, 6g of sodium bicarbonate and 50mL of acetone into a 250mL four-neck flask, add 12.5g of ampicillin in sequence while stirring, cool down to 16°C, and slowly add 1-chloroformyl-3- 6.8 g of methylsulfonyl-2-imidazolidinone was added, and the reaction was continued for another 30 minutes. After complete reaction, 50 mL of isopropyl ether was added for extraction, and the aqueous phase was filtered to a crystallization tank after separation.

[0031] Add 40mL of methyl acetate, cool down to 23°C and slowly add dilute hydrochloric acid dropwise to carry out acidification and crystallization, adjust the pH to 2.2, and stir for 30 minutes under temperature control. . Vacuum -0.08, 50 ° C under reduced pressure drying for 3 hours to obtain 16.0 g of needle crystals.

[0032] Quality index: content 99.2%, single impurity 0.08%, total impurity 0.27%, solvent residue 0.29%.

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Abstract

The invention pertains to the technical field of drug combination preparation, more particularly relates to a preparation technique for mezlocillin. The preparation technique for mezlocillin comprises the following steps: ampicillin trihydrate and 1-chloroformyl-3-methylsulfonyl-2-imidazolidinone carry out acylation reaction under alkaline condition and then extraction, acidification and crystallization are conducted to obtain the mezlocillin. The invention is characterized in that when acylation reaction is conducted, reaction menstruum is water and acetone; after acylation reaction is finished, an ether extractant is added for carrying out extraction; and menthyl acetate is added before acidification so as to carry out acidified crystallization. The synthetic technique has obvious advantages, provides powerful guarantee for synthesizing the mezlocillin with high quality and has relatively great implementation value and long-term social and economic benefit.

Description

(1) Technical field [0001] The invention belongs to the technical field of drug synthesis, in particular to a preparation process of mezlocillin acid. (2) Background technology [0002] Mezlocillin acid is a new type of broad-spectrum semi-synthetic penicillin antibiotics mezlocillin sodium raw material, about the synthesis of mezlocillin acid, two synthetic routes have been reported, starting with 6-aminopenicillanic acid Starting material and two routes with ampicillin trihydrate as starting material. Among them, due to the complex synthesis of the former route, long synthesis route and high cost investment, most enterprises in the country adopt the second route for production. [0003] The original synthesis process using ampicillin trihydrate as the starting material is: add ampicillin trihydrate, water, and ethyl acetate into a four-necked flask, cool down to 16-19°C, add sodium bicarbonate, Add 1-chloroformyl-3-methylsulfonyl-2-imidazolidinone under the same conditio...

Claims

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Application Information

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IPC IPC(8): C07D499/68C07D499/04
Inventor 孙鹏韩振玉郭合广
Owner SHANDONG RUIYING PIONEER PHARMA
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