Alpha-keto-leucine-calcium preparation method

A technology of calcium ketoleucine and calcium chloride, which is applied in the field of preparation of calcium α-ketoleucine, can solve problems such as unsuitability for industrial production, harsh reaction conditions, and difficult availability of raw materials, so as to improve equipment utilization, Easy to get raw materials and stable product quality

Active Publication Date: 2009-12-23
HEBEI YIPIN PHARMA
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Problems solved by technology

[0003] According to literature reports, the synthesis of α-ketoleucine calcium mainly has the following three methods: Route 1 uses isobutyraldehyde and hydantoin (hydantoin) as raw materials, and reacts to generate 5-isobutyraldehyde under the action of an organic base. Butylated hydantoin is then hydrolyzed and acidified under alkaline conditions to generate α-ketoleucine, and then forms calcium salt with calcium chloride to obtain calcium α-ketoleucine; route 2 uses 4-methyl-2 -Pentanone is used as a raw material to generate α-ketoleucine calcium through oxidation and salt formation; route 3 uses 3-methylbutyric acid as a raw material, reacts with

Method used

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  • Alpha-keto-leucine-calcium preparation method

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Example Embodiment

[0019] Example 1:

[0020] a. After mixing 100kg of hydantoin, 15kg of triethylamine and 560kg of water, stir and heat to 80°C, then add 110kg of isobutyraldehyde dropwise within 0.5 hours, then reflux for 7 hours and cool to Stir at 10-30°C to precipitate white solid isobutylidene hydantoin;

[0021] b. At 25°C, add dropwise 960kg of 40% sodium hydroxide (or potassium hydroxide) aqueous solution to the reaction solution at 25°C, stir and heat to 99~101°C for reflux reaction for 5 hours, then cool to room temperature with ice water, Use hydrochloric acid or sulfuric acid with a concentration of 30 to 50% by weight to adjust the pH to ≤2, extract three times with 500 kg of methyl tert-butyl ether solvent, combine the organic phases, and distill off the solvent under reduced pressure to obtain a purple-red liquid α-ketoleucine Crude.

[0022] c. After mixing 850kg of ethanol solution of calcium chloride and 50kg of triethylamine with a concentration of 8% by weight, the crude ...

Example Embodiment

[0023] Embodiment 2: The difference between this embodiment and Example 1 is to replace 15kg triethylamine with 25kg ethanolamine; replace methyl tert-butyl ether solvent with 600kg ether; the methanol solution of calcium chloride (mass percentage concentration is 5%) ) and the diethanolamine of 40kg are mixed.

Example Embodiment

[0024] Embodiment 3: present embodiment and embodiment 1 difference are to replace 15kg triethylamine with 12kg sodium carbonate; Replace methyl tert-butyl ether solvent with 650kg isopropyl ether; A solution of isopropanol and 35kg of ethanolamine are mixed.

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Abstract

The invention discloses an alpha-keto-leucine-calcium preparation method, comprise the following steps: mixing hydantoin, alkali and water and heating the solution, then dripping isobutylaldehyde to perform reflux reaction, cooling the solution after reflux reaction, adding strong alkali liquid and cooling the solution after reflux reaction, extracting and concentrating to obtaining raw liquid alpha-keto-leucine, dripping the raw alpha-keto-leucine in the alcoholic solution of calcium chloride to react and filtrating to obtain alpha-keto-leucine-calcium. The reaction mechanism is as follows: adopting hydantoin to perform condensation reaction with isobutylaldehyde in the presence of catalyst, namely alkali to obtain isobutylidene hydantoin, generating alpha-keto-leucine through hydrolysis in the presence of strong alkali and salifying to obtain alpha-keto-leucine-calcium. The invention adopts condensation reaction so that hydrolysis can be directly realized without separating isobutylidene hydantoin, the equipment utilization can be improved by 30%, the reaction condition is mild and the operation is easier; water is adopted as solvent, thus lowering the cost and waste water and reducing the pollution to the environment; in addition, the invention has accessible raw materials and stable product quality, the reaction yield is increased by 10% compared with that of the prior art, and the invention has no special requirement on the equipment, thus being applicable to the industrial production.

Description

technical field [0001] The invention relates to pharmaceutical and chemical intermediates, in particular to a preparation method of α-ketoleucine calcium. α-ketoleucine is the precursor of the biosynthesis of leucine, an essential amino acid for the human body, and is an important raw material in compound α-ketoacid tablets. In functional drinks, α-ketoleucine and its salts are also important ingredients. technical background [0002] Calcium α-ketoleucine is an important raw material in compound α-keto acid preparations. As one of the normal metabolites of the human body, α-keto acid can also be directly used in the treatment of some uremia. At present, compound α-keto acid preparation combined with low-protein diet therapy can reduce the symptoms of uremia patients and slow down the renal function. Functional deterioration has played a good role. Compound α-ketoacid tablets were developed and marketed by Fresenius Kabi, Germany. Compound α-ketoacid tablets can improve ...

Claims

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Application Information

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IPC IPC(8): C07C59/185C07C51/41C07C51/00
Inventor 刘秀杰张辑钟建西黄瑞明祁振海李培鸿刘亮亮
Owner HEBEI YIPIN PHARMA
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