A method for purifying dimethyl 1,3-acetonedicarboxylate

Abstract

The invention discloses a method for purifying 1,3-acetone dimethyl carboxylate, and belongs to the field of pharmaceutical intermediates. Its preparation method is to dissolve magnesium chloride in water, add 1,3-acetone dimethyl carboxylate crude product and ammonia water, precipitate solid, filter the solid obtained, add organic solvent and water, add acid to adjust to acidity under cooling, extract and dry, rotary evaporation and concentrate the dry solvent, and pump the oil pump to obtain 1,3-acetone dimethyl carboxylate pure product. The present invention crystallizes 1,3-acetone dimethyl carboxylate 90-95% crude product and magnesium chloride into salt and then frees to obtain a purity product of more than 98.5%, which is lower than 97% of the purity on the market. The method reduces production costs and improves product purity.

Description

Technical Field

[0001] The invention relates to a method for purifying dimethyl 1,3-acetone dicarboxylate, and belongs to the technical field of purification of pharmaceutical intermediate products. Background Art

[0002] Dimethyl acetone-1,3-dicarboxylate / 3-oxo-pentanedi oic acid, dimethyl ester (CAS: 1830-54-2), its chemical structure is as follows:

[0003]

[0004] As an important pharmaceutical intermediate, it was used in the synthesis of atropine and scopolamine in the 20th century. In this century, it has been widely used in the synthesis of antibiotic drugs because it has been found to have certain antibacterial activity.

[0005] In the literature reported so far, there are two main methods for preparing 1,3-acetone dicarboxylic acid dimethyl ester: Method A: In CN103288629, it is mainly formed by citric acid catalyzing hydrogen peroxide. In a citric acid aqueous solution, at least one medium-strong acid is used as a catalyst, and hydrogen peroxide is used as a hydrogenating agent. At a fixed temperature, citric acid is oxidized to obtain 1,3-acetone dicarboxylic acid dimethyl ester. This method has a high yield and less pollution, but the purity is generally around 95%. Method B: In CN101475482, citric acid is reacted with 98% concentrated sulfuric acid to obtain acetone dicarboxylic acid, and then anhydrous methanol and thionyl chloride are added to obtain 1,3-acetone dicarboxylic acid dimethyl ester. In this method, the amount of sulfuric acid used is large, and there is great instability in the production process and environmental protection. Summary of the invention

[0006] The object of the present invention is to provide a method for purifying 1,3-acetone dimethyl carboxylate with high purity and low production cost in view of the deficiencies of the prior art. The preparation method is as follows: dissolving magnesium chloride in water, adding crude 1,3-acetone dimethyl carboxylate and ammonia water, and after solids are precipitated, filtering the solids, adding organic solvents and water, adding acid to adjust to acidity under cooling, extracting and drying, rotary evaporation and concentrating the dry solvent, and pumping with an oil pump to obtain pure 1,3-acetone dimethyl carboxylate. The present invention crystallizes the crude 1,3-acetone dimethyl carboxylate with magnesium chloride and then frees it to obtain a product with a purity of more than 98.5%. Compared with products with a purity of less than 97% on the market, this method reduces production costs and improves product purity.

[0007] The technical solution adopted by the present invention is: a method for purifying dimethyl 1,3-acetonedicarboxylate, the method comprising the following steps:

[0008] (3) Dissolve magnesium chloride in water, add crude dimethyl 1,3-acetone dicarboxylate, and stir to form a uniform solution. Then, add aqueous ammonia dropwise to the solution to adjust it to alkalinity. Solids precipitate and filter to obtain the solids.

[0009] (4) adding the obtained solid to a mixed solution of an organic solvent and water, adding acid to adjust the solution to acidity while cooling, extracting and drying; concentrating the organic solvent by rotary evaporation, and pumping dry with an oil pump to obtain pure 1,3-acetone dimethyl dicarboxylate.

[0010] Furthermore, in the above technical solution, in the step (1), the crude content of dimethyl 1,3-acetonedicarboxylate is 90-95%.

[0011] Furthermore, in the above technical solution, in step (1), an organic solvent is added to the reaction, and the organic solvent is acetone, tetrahydrofuran, acetonitrile, dichloromethane or 1,2-dichloroethane.

[0012] Furthermore, in the above technical solution, in the step (1), the ratio of dimethyl 1,3-acetonedicarboxylate, magnesium chloride and aqueous ammonia is 1.105-1.158:1.105-1.158:1.428-1.571.

[0013] Furthermore, in the above technical solution, in the step (1), ammonia water is added to adjust the alkaline pH to 8-10.

[0014] Furthermore, in the above technical solution, in step (2), the acid is added by using dilute hydrochloric acid or dilute sulfuric acid to adjust the pH to 2-3.

[0015] Furthermore, in the above technical solution, in the step (2), the temperature of the dropwise addition is controlled at 0 to 10°C.

[0016] Furthermore, in the above technical solution, in step (2), the organic solvent is selected from dichloromethane, 1,2-dichloroethane or ethyl acetate.

[0017] Furthermore, in the above technical solution, in step (2), anhydrous magnesium sulfate or anhydrous sodium sulfate is used for drying.

[0018] Furthermore, in the above technical solution, in the step (2), the pure product is 1,3-acetone dimethyl carboxylate with a purity of more than 98.5%.

[0019] The beneficial effect of the present invention is that 90-95% crude 1,3-acetone dicarboxylic acid dimethyl ester is used to form salt with magnesium chloride and then crystallize to obtain 1,3-acetone dicarboxylic acid dimethyl ester with a purity of more than 98.5%, thereby reducing production costs and improving product purity. DETAILED DESCRIPTION

[0020] Example 1

[0021] Dissolve 109.3 g MgCl2 (1.148 mol) in water, add 100 g 1,3-acetone dimethyl carboxylate (purity 90%), add 54 g NH3·H2O (concentration 25%) dropwise until pH=8-10 to precipitate solid, continue to add 200 g DCM, stir and filter to obtain solid.

[0022] In another three-necked flask, add the above solid, 150g DCM and 150g H2O, when the temperature drops below 10°C, add 6mol / L HCl to adjust the pH to 2-3, extract twice with 100g DCM, wash with saturated brine until neutral, add anhydrous Na 2 SO 4 After drying, the solvent was concentrated by rotary evaporation and finally pumped dry by oil pump to obtain 85.3 g of product (purity 98.58%, yield 85.3%).

[0023] Example 2

[0024] Dissolve 11.6 g MgCl2 (0.121 mol) in water, add 10 g 1,3-acetone dimethyl carboxylate (purity 90%), add 6 g NH3·H2O (concentration 25%) dropwise until pH=8-10 to precipitate solid, continue to add 200 g DCM, stir and filter to obtain solid.

[0025] In another three-necked flask, add the above solid, 30g DCM and 30g H2O, and when the temperature drops below 10°C, add 6mol / L HCl to adjust the pH to 2-3. After extracting twice with 100g DCM, wash with saturated brine until neutral, and add anhydrous Na 2 SO 4 After drying, the solvent was concentrated by rotary evaporation and finally pumped dry by oil pump to obtain 8 g of product (purity 98.55%, yield 80%).

[0026] Example 3

[0027] Dissolve 51.2g MgCl2 (0.537mol) in water, add 49g 1,3-acetone dimethyl carboxylate (purity 90%), add 45g NH3·H2O (concentration 25%) dropwise until pH=8-10 to precipitate solid, continue to add 200g DCM, stir and filter to obtain solid.

[0028] In another three-necked flask, add the above solid, 84g DCM and 84g H2O, and when the temperature drops below 10°C, add 6mol / L HCl to adjust the pH to 2-3, extract twice with 100g DCM, wash with saturated brine until neutral, and add anhydrous Na 2 SO4 After drying, the solvent was concentrated by rotary evaporation and finally pumped dry by oil pump to obtain 43 g of product (purity 98.23%, yield 87.7%).

[0029] Example 4

[0030] Dissolve 85.1g MgCl2 (0.893mol) in water, add 79g 1,3-acetone dimethyl carboxylate (purity 92%), add 80g NH3·H2O (concentration 25%) dropwise until pH=8-10 to precipitate solid, continue to add 200g DCM, stir and filter to obtain solid.

[0031] In another three-necked flask, add the above solid, 102g DCM and 102g H2O, and when the temperature drops below 10°C, add 6mol / L HCl to adjust the pH to 2-3, extract twice with 100g DCM, wash with saturated brine until neutral, and add anhydrous Na 2 SO 4 After drying, the solvent was concentrated by rotary evaporation and finally pumped dry by oil pump to obtain 71 g of product (purity 99.49%, yield 89.8%).

[0032] The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical solution and inventive concept of the present invention within the technical protection scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims

1. A method for purifying dimethyl 1,3-acetonedicarboxylate, It is characterized in that The steps include: (1) dissolving magnesium chloride in water, adding crude 1,3-acetone dimethyl ester, stirring to form a uniform solution, then dropping ammonia water into the solution to adjust the pH to alkaline = 8-10, solid precipitates, adding organic solvent dichloromethane, filtering to obtain a solid; (2) Add the obtained solid to a mixed solution of an organic solvent of dichloromethane and water, add dilute hydrochloric acid dropwise to adjust the pH value to 2-3 while cooling the solid to control the temperature at 0-10°C, extract and dry; concentrate the organic solvent dichloromethane by rotary evaporation, and pump dry with an oil pump to obtain pure 1,3-acetone dimethyl ester.

2. The method for purifying dimethyl 1,3-acetonedicarboxylate according to claim 1, Features: In step (1), the crude content of dimethyl 1,3-acetonedicarboxylate is 90-95%.

3. The method for purifying dimethyl 1,3-acetonedicarboxylate according to claim 1, Features: In step (2), anhydrous magnesium sulfate or anhydrous sodium sulfate is used for drying.

4. A method for purifying dimethyl 1,3-acetonedicarboxylate according to any one of claims 1 to 3, Features: In step (2), the pure product is 1,3-acetone dimethyl carboxylate with a purity of more than 98.5%.

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