WO2020140309A1 - Method for preparing 3-hydroxybutyrate amino acid salt compound - Google Patents
Method for preparing 3-hydroxybutyrate amino acid salt compound Download PDFInfo
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- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/41—Preparation of salts of carboxylic acids
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- C07C59/01—Saturated compounds having only one carboxyl group and containing hydroxy or O-metal groups
Abstract
The present invention provides a method for preparing a 3-hydroxybutyrate amino acid salt compound, comprising: (1) adding ethyl 3-hydroxybutyrate or methyl 3-hydroxybutyrate into a reaction vessel, taking water as a solvent, adding a base catalyst, and hydrolyzing ethyl 3-hydroxybutyrate or methyl 3-hydroxybutyrate under the effect of the base catalyst to obtain 3-hydroxybutyrate; and (2) adding 3-hydroxybutyrate into the reaction vessel, adding ethyl alcohol as the solvent, then adding natural amino acid, and enabling 3-hydroxybutyrate and natural amino acid to react for 12-24 hours under the temperature at 30-80°C to obtain the 3-hydroxybutyrate amino acid salt compound. According to the present invention, some purification processes are omitted, the operation is convenient, and raw materials are saved. In the mode of salifying in ethyl alcohol according to the present invention, reaction is more thorough, reaction time is saved, energy consumption and material loss are reduced, product yield is increased, and production costs are greatly saved.
Description
本发明涉及化工技术领域，具体涉及一种制备3-羟基丁酸氨基酸盐复合物的方法。The invention relates to the technical field of chemical industry, in particular to a method for preparing a 3-hydroxybutyric acid amino acid salt complex.
β-羟基丁酸氨基酸盐会被吸收到血液中，在那里它会分解出游离的氨基酸和β-羟基丁酸。由于β-羟基丁酸是一种水基溶液，因此食用该产品会在血液中添加更多酮类，这可以让食用者的身体获得更好的能量产生。β-羟基丁酸与氨基酸结合时很稳定，它通过制造酮所需的额外氨基酸营养素提供额外的益处。The β-hydroxybutyric acid amino acid salt will be absorbed into the blood, where it will break down free amino acids and β-hydroxybutyric acid. Because β-hydroxybutyric acid is a water-based solution, eating this product will add more ketones to the blood, which can allow the body of the consumer to get better energy production. Beta-hydroxybutyric acid is very stable when combined with amino acids, and it provides additional benefits through the extra amino acid nutrients needed to make ketones.
3-羟基丁酸分子中含有羟基和羧基两种官能团，具有醇和羧基的综合性能，是一种重要的制药原料和药理学试剂。其中(R)-3-羟基丁酸是3-羟基丁酸外消旋体中的R-构型的异构体，是一种具有光学活性的手性化合物，CAS号为625-72-9。(R)-3-羟基丁酸是哺乳动物体内由肝脏内的长链脂肪酸代谢而产生的化合物，作为主要的酮体存在于血浆和外周组织中，在人体外周组织具有很好的渗透能力及快速扩散能力，可以用作身体大部分组织中的能量来源。一般地，R-3-HB多以各种盐的形式存在。(R)-3-羟基丁酸除了具有营养功能之外，还具有治疗许多疾病的作用，包括：可以治疗许多得益于酮体水平提高的疾病(如包括癫痫和肌阵挛的神经紊乱疾病以及包括阿尔兹默症和痴呆等的神经退化性疾病)；通过氧化辅酶Q来减少自由基伤害(如缺血症)；加强代谢效率(提高训练效率以及运动成绩，治疗供养不足、心绞痛、心肌梗塞等)；治疗如癌症尤其是脑癌(如星细胞瘤等)相关的疾病；对于糖代谢紊乱(如I型糖尿病、II型糖尿病、低血糖低酮体症等)具有很好的疗效；可以用于防治骨质减少、骨质疏松症、重度骨质疏松症以及相关骨折等。基于这些功能，(R)-3-羟基丁酸及其盐可以用作食品添加剂和药物，具有巨大的保健和药用价值。3-Hydroxybutyric acid molecule contains two functional groups, hydroxyl and carboxyl, with the comprehensive performance of alcohol and carboxyl, it is an important pharmaceutical raw material and pharmacological reagent. Among them, (R)-3-hydroxybutyric acid is the isomer of R-configuration in the racemic form of 3-hydroxybutyric acid, which is an optically active chiral compound, CAS number is 625-72-9 . (R)-3-Hydroxybutyric acid is a compound produced by the metabolism of long-chain fatty acids in the liver in mammals. It is present in the plasma and peripheral tissues as the main ketone body. It has good permeability and The ability of rapid diffusion can be used as an energy source in most tissues of the body. Generally, R-3-HB exists in the form of various salts. In addition to its nutritional function, (R)-3-hydroxybutyric acid has the effect of treating many diseases, including: it can treat many diseases that benefit from the increase of ketone body levels (such as neurological disorders including epilepsy and myoclonus) And neurodegenerative diseases including Alzheimer's disease and dementia); reducing free radical damage by oxidizing coenzyme Q (such as ischemia); enhancing metabolic efficiency (improving training efficiency and athletic performance, treating insufficient support, angina, myocardium Infarction, etc.); treatment of diseases related to cancer, especially brain cancer (such as astrocytoma, etc.); has a good effect on glucose metabolism disorders (such as type I diabetes, type II diabetes, hypoglycemia and low ketosis, etc.); It can be used to prevent and treat osteopenia, osteoporosis, severe osteoporosis and related fractures. Based on these functions, (R)-3-hydroxybutyric acid and its salts can be used as food additives and medicines, and have great health care and medicinal value.
(R)-3-羟基丁酸的制备主要为化学法和微生物法。现有技术的化学合成法的缺点主要是产物的光学纯度相对较低，即对映体过量值(ee值)相对较低。微生物发酵法可直接得到R-3-HB；或者先采用微生物合成聚R-3-HB，然后降解该聚合物得到R-3-HB，微生物法的产物ee值较高，但由于工艺均较复杂，生产投入大，导致R-3-HB的成本和价格居高不下。The preparation of (R)-3-hydroxybutyric acid is mainly chemical method and microbiological method. The shortcoming of the prior art chemical synthesis method is that the optical purity of the product is relatively low, that is, the enantiomeric excess value (ee value) is relatively low. Microbial fermentation method can directly obtain R-3-HB; or first use microorganisms to synthesize poly R-3-HB, and then degrade the polymer to obtain R-3-HB, the product of microbe method has a higher ee value, but because the process is relatively The complexity and large investment in production have led to high costs and prices of R-3-HB.
发明内容Summary of the invention
本发明的目的是为了提供一种制备3-羟基丁酸氨基酸盐复合物的方法，可以降低成本，且收率高。The purpose of the present invention is to provide a method for preparing a 3-hydroxybutyric acid amino acid salt complex, which can reduce costs and has a high yield.
本发明的目的是通过以下技术方案实现的：The purpose of the present invention is achieved by the following technical solutions:
一种制备3-羟基丁酸氨基酸盐复合物的方法，包括：A method for preparing 3-hydroxybutyric acid amino acid salt complex, including:
(1)在反应容器中加入3-羟基丁酸乙酯或3-羟基丁酸甲酯，并加入水作为溶剂，然后加入碱催化剂，3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂的摩尔比为1:2.5～4.5；3-羟基丁酸乙酯或3-羟基丁酸甲酯和碱催化剂反应，3-羟基丁酸乙酯或3-羟基丁酸甲酯经碱催化水解得3-羟基丁酸；(1) Add 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester to the reaction vessel, and add water as a solvent, then add the base catalyst, 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester The molar ratio with alkali catalyst is 1:2.5～4.5; 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester reacts with alkali catalyst, 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester reacts with alkali Catalytic hydrolysis to obtain 3-hydroxybutyric acid;
(2)将步骤(1)中得到的3-羟基丁酸加入反应容器中，加入乙醇作为溶剂，再加入天然氨基酸，3-羟基丁酸与天然氨基酸的摩尔比为1～1.1:1.5；3-羟基丁酸与天然氨基酸在30-80℃温度下，反应12-24小时，得到3-羟基丁酸氨基酸盐复合物。(2) Add 3-hydroxybutyric acid obtained in step (1) to the reaction vessel, add ethanol as a solvent, and then add natural amino acids, the molar ratio of 3-hydroxybutyric acid to natural amino acids is 1 ~ 1.1:1.5; 3 -Hydroxybutyric acid and natural amino acids are reacted at a temperature of 30-80°C for 12-24 hours to obtain a 3-hydroxybutyric acid amino acid salt complex.
进一步，步骤(1)中，所述碱催化剂选自氢氧化钠、氢氧化钾、氢氧化锂中的一种或多种。Further, in step (1), the alkali catalyst is selected from one or more of sodium hydroxide, potassium hydroxide, and lithium hydroxide.
进一步，步骤(1)中，3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂反应的时间为3-12小时。Further, in step (1), the reaction time of ethyl 3-hydroxybutyrate or methyl 3-hydroxybutyrate with an alkali catalyst is 3-12 hours.
进一步，步骤(1)中，还包括：3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂反应后，经减压蒸馏除去水；再加入乙醇充分搅拌分散降温至0℃以下析晶，并在0℃-5℃之间保温12小时以上，抽滤分离出固体，用乙醇洗涤固体，干燥，即得到3-羟基丁酸。Further, step (1) further includes: after the reaction of 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester with an alkali catalyst, the water is distilled off under reduced pressure; then ethanol is added to fully stir to disperse and cool down to below 0°C Crystallize and incubate at 0℃-5℃ for more than 12 hours, separate the solid by suction filtration, wash the solid with ethanol, and dry to obtain 3-hydroxybutyric acid.
进一步，步骤(2)中，所述天然氨基酸选自丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、色氨酸、蛋氨酸、甘氨酸、丝氨酸、苏氨酸、半胱氨酸、酪氨酸、天冬酰胺、谷氨酰胺、赖氨酸、精氨酸、组氨酸、天冬氨酸、谷氨酸中的一种或多种。Further, in step (2), the natural amino acid is selected from alanine, valine, leucine, isoleucine, proline, phenylalanine, tryptophan, methionine, glycine, serine, One or more of threonine, cysteine, tyrosine, asparagine, glutamine, lysine, arginine, histidine, aspartic acid, and glutamic acid.
进一步，步骤(2)中，还包括：3-羟基丁酸与天然氨基酸反应完毕后，进行过滤，在滤液中加入活性炭进行脱色，再过滤后，经减压蒸馏除去乙醇；再加入异丙醇充分搅拌分散，降温至0℃以下析晶，并在0℃-5℃之间保温24小时以上抽滤分离出固体，干燥后即得到3-羟基丁酸氨基酸盐复合物。Further, step (2) further includes: after the reaction of 3-hydroxybutyric acid and natural amino acids is completed, filtering is performed, activated carbon is added to the filtrate for decolorization, and after filtering, ethanol is distilled off under reduced pressure; then isopropyl alcohol is added Stir and disperse thoroughly, lower the temperature to below 0℃ and crystallize, and keep it at 0℃-5℃ for more than 24 hours to separate the solid by suction filtration. After drying, the 3-hydroxybutyric acid amino acid salt complex is obtained.
进一步，所述活性炭的重量为3-羟基丁酸重量的20％。Further, the weight of the activated carbon is 20% of the weight of 3-hydroxybutyric acid.
综上所述，由于采用了上述技术方案，本发明与现有技术相比，有以下优点：In summary, compared with the prior art, the present invention has the following advantages due to the adoption of the above technical solutions:
本发明提供了一种制备3-羟基丁酸氨基酸盐复合物的新方法，以3-羟基丁酸乙酯或3-羟基丁酸甲酯为原料与催化剂反应，制备3-羟基丁酸后与天然氨基酸成盐，得到3-羟基丁酸氨基酸盐复合物。省略部分提纯过程，操作方便，可以节约原材料。本发明采用乙醇中成盐的方式，使反应进行的更彻底，不仅节省了反应时间，还降低了能耗及物料损失，提高了产品收率，大大节约了生产成本。The present invention provides a new method for preparing 3-hydroxybutyric acid amino acid salt complex. It takes 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester as raw materials and reacts with the catalyst. Natural amino acids are salted to obtain 3-hydroxybutyric acid amino acid salt complexes. Omitting part of the purification process is easy to operate and can save raw materials. The invention adopts the salt-forming method in ethanol to make the reaction more thorough, which not only saves the reaction time, but also reduces the energy consumption and material loss, improves the product yield, and greatly saves the production cost.
本发明省略了3-羟基丁酸氨基酸盐复合物粗品制备的浓水过程，以及3-羟基丁酸氨基酸盐复合物成品的无水异丙醇精制浓缩、加丙酮析晶、过滤、洗涤、干燥等一系列过程，不仅省去了有机溶剂丙酮，而且节约了相应过程的物料损失和能源消耗，大幅度降低了3-羟基丁 酸成氨基酸络合物的生产成本。减少了3-羟基丁酸氨酸酸络合物的粗制及精制中的受热过程,水中成氨基酸络合物也避免了3-羟基丁酸络合物成品易吸潮的问题,保证了3-羟基丁酸氨酸酸络合物的质量。The invention omits the concentrated water process for preparing the crude product of 3-hydroxybutyric acid amino acid salt complex, and the refined concentration of anhydrous isopropanol of the finished product of 3-hydroxybutyric acid amino acid salt complex, crystallization with acetone, filtration, washing and drying Waiting for a series of processes not only saves the organic solvent acetone, but also saves the material loss and energy consumption of the corresponding process, and greatly reduces the production cost of 3-hydroxybutyric acid into an amino acid complex. Reduces the heating process in the crude and refining of 3-hydroxybutyric acid complexes. The formation of amino acid complexes in water also avoids the problem of easy absorption of moisture in the finished 3-hydroxybutyric acid complexes, ensuring 3 -The quality of hydroxybutyric acid complex.
下面对本发明的具体实施方式作进一步详细介绍。The specific implementation of the present invention will be described in further detail below.
实施例1Example 1
将200克水加入反应容器中，搅拌下加入130克3-羟基丁酸乙酯，待3-羟基丁酸乙酯彻底溶解后，166克加入氢氧化锂，然后升温至35℃，恒温反应24小时。反应完毕后，减压蒸馏除去水；降温至0℃，加入乙醇，充分搅拌分散2小时，降温至0℃以下析晶，并在0℃-5℃之间保温12小时以上，抽滤分离，用乙醇洗涤固体，于35℃下干燥，即获得147克3-羟基丁酸成品，收率90.1％。Add 200 grams of water to the reaction vessel, add 130 grams of ethyl 3-hydroxybutyrate with stirring. After the 3-hydroxybutyric acid ethyl ester is completely dissolved, add 166 grams of lithium hydroxide, and then warm to 35 ℃, constant temperature reaction 24 hour. After the reaction is completed, the water is distilled off under reduced pressure; the temperature is reduced to 0°C, ethanol is added, and the mixture is fully stirred and dispersed for 2 hours, the temperature is reduced to below 0°C, and the crystal is incubated at 0°-5°C for more than 12 hours, and separated by suction filtration. The solid was washed with ethanol and dried at 35°C to obtain 147 g of 3-hydroxybutyric acid product with a yield of 90.1%.
取147克3-羟基丁酸成品加入反应容器中，再加入乙醇，搅拌溶解，加入75克L-赖氨酸，然后升温至45℃恒温反应12小时。反应完毕后，温度70℃以下蒸馏除去乙醇，降温至0℃,加入异丙醇充分搅拌分散，降温至0℃以下析晶，并在0℃-5℃之间保温24小时以上，抽滤分离，用异丙醇洗涤固体，35℃下干燥，即获得165克3-羟基丁酸赖氨酸盐复合物成品，收率为92％。Take 147 grams of 3-hydroxybutyric acid product into the reaction vessel, add ethanol, stir to dissolve, add 75 grams of L-lysine, and then warm to 45 ℃ constant temperature reaction for 12 hours. After the reaction is completed, the ethanol is distilled off at a temperature below 70°C, the temperature is lowered to 0°C, isopropyl alcohol is added to fully stir and disperse, the temperature is reduced to below 0°C to crystallize, and the temperature is kept between 0°C-5°C for more than 24 hours, and the filter is separated by suction After washing the solid with isopropanol and drying at 35°C, 165 g of 3-hydroxybutyric acid lysine salt composite product was obtained with a yield of 92%.
实施例2Example 2
将200克水加入反应容器中，搅拌下加入130克3-羟基丁酸甲酯，待3-羟基丁酸甲酯彻底溶解后，166克加入氢氧化锂，然后升温至35℃，恒温反应24小时。反应完毕后，减压蒸馏除去水；降温至0℃，加入乙醇，充分搅拌分散2小时，降温至0℃以下析晶，并在0℃-5℃之间保温12小时以上，抽滤分离，用乙醇洗涤固体，于35℃下干燥，即获得147克3-羟基丁酸成品，收率90.1％。Add 200 grams of water to the reaction vessel, add 130 grams of 3-hydroxybutyric acid methyl ester with stirring. After the 3-hydroxybutyric acid methyl ester is completely dissolved, add 166 grams of lithium hydroxide, and then warm to 35 ℃, constant temperature reaction 24 hour. After the reaction is completed, the water is distilled off under reduced pressure; the temperature is reduced to 0°C, ethanol is added, and the mixture is fully stirred and dispersed for 2 hours, the temperature is reduced to below 0°C, and the crystal is incubated at 0°-5°C for more than 12 hours, and separated by suction filtration. The solid was washed with ethanol and dried at 35°C to obtain 147 g of 3-hydroxybutyric acid product with a yield of 90.1%.
取147克3-羟基丁酸成品加入反应容器中，再加入乙醇，搅拌溶解，加入75克L-赖氨酸，然后升温至45℃恒温反应12小时。反应完毕后，温度70℃以下蒸馏除去乙醇，降温至0℃,加入异丙醇充分搅拌分散，降温至0℃以下析晶，并在0℃-5℃之间保温24小时以上，抽滤分离，用异丙醇洗涤固体，35℃下干燥，即获得165克3-羟基丁酸赖氨酸盐复合物成品，收率为92％。Take 147 grams of 3-hydroxybutyric acid product into the reaction vessel, add ethanol, stir to dissolve, add 75 grams of L-lysine, and then warm to 45 ℃ constant temperature reaction for 12 hours. After the reaction is completed, the ethanol is distilled off at a temperature below 70°C, the temperature is lowered to 0°C, isopropyl alcohol is added to fully stir and disperse, the temperature is reduced to below 0°C to crystallize, and the temperature is kept between 0°C-5°C for more than 24 hours, and the filter is separated by suction After washing the solid with isopropanol and drying at 35°C, 165 g of 3-hydroxybutyric acid lysine salt composite product was obtained with a yield of 92%.
以上所述的实施例仅用于说明本发明的技术思想及特点，其目的在于使本领域内的技术人员能够了解本发明的内容并据以实施，不能仅以本实施例来限定本发明的专利范围，即凡依本发明所揭示的精神所作的同等变化或修饰，仍落在本发明的专利范围内。The above-mentioned embodiments are only used to explain the technical ideas and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the contents of the present invention and implement them accordingly. The patent scope, that is, any equivalent changes or modifications made in accordance with the spirit disclosed by the present invention, still falls within the patent scope of the present invention.
Claims (7)
- 一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，包括：A method for preparing 3-hydroxybutyric acid amino acid salt complex, characterized in that it includes:(1)在反应容器中加入3-羟基丁酸乙酯或3-羟基丁酸甲酯，并加入水作为溶剂，然后加入碱催化剂，3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂的摩尔比为1:2.5～4.5；3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂反应，3-羟基丁酸乙酯或3-羟基丁酸甲酯经碱催化水解得3-羟基丁酸；(1) Add 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester to the reaction vessel, and add water as a solvent, then add the base catalyst, 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester The molar ratio with alkali catalyst is 1:2.5～4.5; 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester reacts with alkali catalyst, 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester reacts with alkali Catalytic hydrolysis to obtain 3-hydroxybutyric acid;(2)将步骤(1)中得到的3-羟基丁酸加入反应容器中，加入乙醇作为溶剂，再加入天然氨基酸，3-羟基丁酸与天然氨基酸的摩尔比为1～1.1:1.5；3-羟基丁酸与天然氨基酸在30-80℃温度下，反应12-24小时，得到3-羟基丁酸氨基酸盐复合物。(2) Add 3-hydroxybutyric acid obtained in step (1) to the reaction vessel, add ethanol as a solvent, and then add natural amino acids, the molar ratio of 3-hydroxybutyric acid to natural amino acids is 1 ~ 1.1:1.5; 3 -Hydroxybutyric acid and natural amino acids are reacted at a temperature of 30-80°C for 12-24 hours to obtain a 3-hydroxybutyric acid amino acid salt complex.
- 根据权利要求1所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，步骤(1)中，所述碱催化剂选自氢氧化钠、氢氧化钾、氢氧化锂中的一种或多种。The method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 1, wherein in step (1), the alkali catalyst is selected from sodium hydroxide, potassium hydroxide, and lithium hydroxide One or more.
- 根据权利要求1所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，步骤(1)中，3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂反应的时间为3-12小时。A method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 1, wherein in step (1), ethyl 3-hydroxybutyrate or methyl 3-hydroxybutyrate and an alkali catalyst The reaction time is 3-12 hours.
- 根据权利要求1所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，步骤(1)中，还包括：3-羟基丁酸乙酯或3-羟基丁酸甲酯与碱催化剂反应后，经减压蒸馏除去水；再加入乙醇充分搅拌分散降温至0℃以下析晶，并在0℃-5℃之间保温12小时以上，抽滤分离出固体，用乙醇洗涤固体，干燥，即得到3-羟基丁酸。The method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 1, wherein step (1) further comprises: 3-hydroxybutyric acid ethyl ester or 3-hydroxybutyric acid methyl ester After reacting with the alkali catalyst, the water is distilled off under reduced pressure; then add ethanol to fully stir and disperse and reduce the temperature to below 0 ℃ and crystallize, and keep at 0 ℃-5 ℃ for more than 12 hours, the solid is separated by suction filtration and washed with ethanol Solid, dried to obtain 3-hydroxybutyric acid.
- 根据权利要求1所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，步骤(2)中，所述天然氨基酸选自丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、色氨酸、蛋氨酸、甘氨酸、丝氨酸、苏氨酸、半胱氨酸、酪氨酸、天冬酰胺、谷氨酰胺、赖氨酸、精氨酸、组氨酸、天冬氨酸、谷氨酸中的一种或多种。The method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 1, wherein in step (2), the natural amino acid is selected from alanine, valine, leucine, Isoleucine, proline, phenylalanine, tryptophan, methionine, glycine, serine, threonine, cysteine, tyrosine, asparagine, glutamine, lysine, sperm One or more of histidine, histidine, aspartic acid, and glutamic acid.
- 根据权利要求1所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，步骤(2)中，还包括：3-羟基丁酸与天然氨基酸反应完毕后，进行过滤，在滤液中加入活性炭进行脱色，再过滤后，经减压蒸馏除去乙醇；再加入异丙醇充分搅拌分散，降温至0℃以下析晶，并在0℃-5℃之间保温24小时以上抽滤分离出固体，干燥后即得到3-羟基丁酸氨基酸盐复合物。The method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 1, wherein step (2) further comprises: filtering the 3-hydroxybutyric acid and the natural amino acid after the reaction is completed, Activated carbon is added to the filtrate for decolorization, and after filtration, ethanol is distilled off under reduced pressure; isopropanol is then added to fully stir and disperse, the temperature is reduced to below 0 ℃ and crystallized, and the temperature is kept between 0 ℃ and 5 ℃ for more than 24 hours. The solid was separated by filtration, and the 3-hydroxybutyric acid amino acid salt complex was obtained after drying.
- 根据权利要求6所述的一种制备3-羟基丁酸氨基酸盐复合物的方法，其特征在于，所述活性炭的重量为3-羟基丁酸重量的20％。A method for preparing a 3-hydroxybutyric acid amino acid salt complex according to claim 6, wherein the weight of the activated carbon is 20% of the weight of 3-hydroxybutyric acid.
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