Alpha-keto-leucine-calcium preparation method

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 ...

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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 diethyl cyanophosphate, and then undergoes hydrolysis, oxidation and salt formation The reaction obtains α-ketoleucine calcium. Comparing these three methods, it is found that the equipment utilization rate of the synthetic route 1 is low, requires two-step reaction, takes up a lot of equipment, takes a lot of time, and the yield is low, which is 10 times lower than that of the one-pot method. percentage point

Synthetic routes 2 and 3, the raw materials are not easy to obtain, the operation is complicated, the reaction conditions are harsh, the cost is high, and the environmental pollution is also large, so it is not suitable for industrial production

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