CN1373125A - Process for preparing D-proline - Google Patents
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- CN1373125A CN1373125A CN 02112697 CN02112697A CN1373125A CN 1373125 A CN1373125 A CN 1373125A CN 02112697 CN02112697 CN 02112697 CN 02112697 A CN02112697 A CN 02112697A CN 1373125 A CN1373125 A CN 1373125A
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- ONIBWKKTOPOVIA-SCSAIBSYSA-N D-Proline Chemical compound OC(=O)[C@H]1CCCN1 ONIBWKKTOPOVIA-SCSAIBSYSA-N 0.000 title claims abstract description 31
- 229930182820 D-proline Natural products 0.000 title claims abstract description 31
- 238000004519 manufacturing process Methods 0.000 title abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 229960002429 proline Drugs 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 13
- 229930182821 L-proline Natural products 0.000 claims abstract description 9
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000012452 mother liquor Substances 0.000 claims abstract description 8
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims abstract description 6
- 150000007524 organic acids Chemical class 0.000 claims abstract description 5
- 239000005457 ice water Substances 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- FEWJPZIEWOKRBE-LWMBPPNESA-L D-tartrate(2-) Chemical compound [O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O FEWJPZIEWOKRBE-LWMBPPNESA-L 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 4
- -1 E Chemical compound 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 2
- 150000001299 aldehydes Chemical class 0.000 claims 2
- 238000001816 cooling Methods 0.000 claims 1
- NGPGDYLVALNKEG-OTWIGTIJSA-N diazanium;(2s,3s)-2,3-dihydroxybutanedioate Chemical compound [NH4+].[NH4+].[O-]C(=O)[C@@H](O)[C@H](O)C([O-])=O NGPGDYLVALNKEG-OTWIGTIJSA-N 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract description 13
- 229960001270 d- tartaric acid Drugs 0.000 abstract description 12
- 239000003054 catalyst Substances 0.000 abstract description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 abstract description 2
- 229940024606 amino acid Drugs 0.000 description 8
- 150000001413 amino acids Chemical class 0.000 description 8
- 239000002904 solvent Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000126 substance Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 230000006340 racemization Effects 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- NGPGDYLVALNKEG-UHFFFAOYSA-N azanium;azane;2,3,4-trihydroxy-4-oxobutanoate Chemical compound [NH4+].[NH4+].[O-]C(=O)C(O)C(O)C([O-])=O NGPGDYLVALNKEG-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 150000008574 D-amino acids Chemical class 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000012069 chiral reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004064 recycling Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000012805 post-processing Methods 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- FBVVGPMIPAZFAW-KRSQWWHXSA-N (2s)-pyrrolidine-2-carboxylic acid;(2r)-pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@H]1CCCN1.OC(=O)[C@@H]1CCCN1 FBVVGPMIPAZFAW-KRSQWWHXSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000011426 transformation method Methods 0.000 description 1
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- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
一种制备D－脯氨酸的方法,本方法是一种成本低、后处理容易、适合于大批量生产的D－脯氨酸制备方法,其步骤为:a．将L－脯氨酸与D－酒石酸混合并溶于有机酸中,b．加入10～30%的醛类催化剂,在80±10℃的条件下搅拌4～8小时,c．用冰水浴冷却,过滤,用无水乙醇洗涤、干燥,d．粗盐用乙醇中重结晶,得到D－酒石酸·D脯氨酸精盐,e．将D－酒石酸·D－脯氨酸精盐溶于甲醇中,f．在20～65℃的条件下,搅拌并加入氨化剂至溶液呈弱碱性,g．在室温下搅拌后,冷却至5～10℃,过滤出D－酒石酸铵盐,h．母液蒸去甲醇后,重结晶,得到D－脯氨酸。L－脯氨酸与D－酒石酸的混合比例为1∶1。A method for preparing D-proline. This method is a method for preparing D-proline with low cost, easy post-treatment and suitable for mass production. The steps are: a. Mix L-proline and D-tartaric acid and dissolve in organic acid, b. Add 10-30% aldehyde catalyst and stir for 4-8 hours at 80±10°C, c. Cool in an ice-water bath, filter, wash with absolute ethanol, and dry, d. Coarse salt is recrystallized from ethanol to obtain D-tartaric acid · D proline refined salt, e. Dissolve D-tartaric acid·D-proline refined salt in methanol, f. Under the condition of 20～65℃, stir and add ammoniating agent until the solution is weakly alkaline, g. After stirring at room temperature, cool to 5 ~ 10 ℃, filter D-ammonium tartrate, h. After distilling off methanol from the mother liquor, recrystallize to obtain D-proline. The mixing ratio of L-proline and D-tartaric acid is 1:1.
Description
一、技术领域：1. Technical field:
本发明是一种制备手性有机化合物的方法，尤其是一种制备D-脯氨酸的方法。The invention is a method for preparing chiral organic compounds, especially a method for preparing D-proline.
二、背景技术：2. Background technology:
D-氨基酸是一类重要的手性试剂和手性中间体。目前D-氨基酸的生产，多数是用合成方法制备外消旋体，然后进行拆分得到旋光异构体。因此，外消旋氨基酸的拆分是D-氨基酸生产中的一个重要的步骤。D-amino acid is an important class of chiral reagents and chiral intermediates. At present, most of the production of D-amino acid is to prepare the racemate by synthetic method, and then carry out the resolution to obtain the optical isomer. Therefore, the resolution of racemic amino acids is an important step in the production of D-amino acids.
外消旋氨基酸最常用的拆分方法之一是化学拆分法，即使外消旋氨基酸与手性试剂作用生成非对映体，利用非对映体物理、化学性质的差异而将它们分开。氨基酸既含有酸性基团，又含有碱性基团，是两性化合物，因此最方便的方法是使其与不对称的酸或碱作用，生成两种非对映体的盐，利用盐在溶剂中的溶解度的差异，通过重结晶的方法将它们分开，分开后的非对映体，用常用的酸或碱中和，就可以得到旋光氨基酸，同时，游离出手性的酸或碱，循环使用。One of the most commonly used separation methods for racemic amino acids is the chemical resolution method. Even if the racemic amino acid reacts with a chiral reagent to form diastereomers, they are separated by utilizing the differences in physical and chemical properties of the diastereomers. Amino acids contain both acidic groups and basic groups, and are amphoteric compounds. Therefore, the most convenient way is to make them react with asymmetric acids or bases to generate two diastereomeric salts. Due to the difference in solubility, they are separated by recrystallization, and the separated diastereomers are neutralized with common acids or bases to obtain optically active amino acids. At the same time, chiral acids or bases are freed for recycling.
然而，通过普通化学拆分法最多只能得到50％D-型旋光活性氨基酸，另外50％则是L-型异构体。为了提高拆分收率，需要将L-型氨基酸通过消旋化的方法转变成外消旋体然后循环使用。这种方法有下述缺点：总收率较低；在拆分步骤中，会有非对映异构体的夹带析出，致使旋光纯度降低；增加一个消旋化步骤，工序增加，各方面的消耗增加。However, only 50% of D-type optically active amino acids can be obtained by ordinary chemical resolution methods, and the other 50% are L-type isomers. In order to improve the resolution yield, it is necessary to convert the L-type amino acid into a racemate by racemization and then recycle it. This method has the following disadvantages: the total yield is low; in the resolution step, there will be entrainment and separation of diastereoisomers, resulting in a reduction in optical purity; adding a racemization step, the operation increases, and various aspects Consumption increases.
另一种拆分方法是不对称转换，是改进的化学拆分法。不对称转换工艺作为光学活性化合物的先进的拆分方法，是将过饱体系中非对映异构体的结晶和对映异构体消旋化相结合，使结晶、拆分和消旋(one-pot)，把外消旋体混合物转化为一种光学异构体，这种方法省去了经典拆分中的消旋化的步骤，避免了另一种对映体的损失，使拆分效率大大的提高；也避免了经典化学拆分中因对映体浓度增加而导致的夹带析出现象，使光学纯度得到了保证。D-脯氨酸(proline)是合成各种光学活性化合物、吡咯烷衍生物的重要中间体，也是重要的手性试剂之一。制备D-脯氨酸方法一般是先合成外消旋脯氨酸，然后用化学方法拆分。由于外消旋脯氨酸其合成困难，因此拆分所得D-脯氨酸价格昂贵。L-脯氨酸可以从天然蛋白质中分离提取，廉价易得，D-脯氨酸与L-脯氨酸的价格比相差较大，因此，通过不对称转化由L-脯氨酸制备D-脯氨酸具有非常重要的意义。日本人SHIRAIWA等曾经报道不对称转化方法制备D-脯氨酸工艺，但是原料和溶剂消耗多，不容易得到纯品，在工业生产上没有实际意义，Another resolution method is asymmetric conversion, which is an improved chemical resolution method. As an advanced resolution method for optically active compounds, the asymmetric conversion process combines the crystallization of diastereoisomers and the racemization of enantiomers in a supersaturated system to make crystallization, resolution and racemization ( One-pot), the racemic mixture is converted into an optical isomer, this method saves the step of racemization in the classical resolution, avoids the loss of another enantiomer, and makes the resolution The separation efficiency is greatly improved; the entrainment and precipitation phenomenon caused by the increase of enantiomer concentration in the classical chemical resolution is also avoided, so that the optical purity is guaranteed. D-proline (proline) is an important intermediate in the synthesis of various optically active compounds and pyrrolidine derivatives, and is also one of the important chiral reagents. The method for preparing D-proline is generally to synthesize racemic proline first, and then resolve it by chemical methods. Due to the difficulty in the synthesis of racemic proline, the resulting D-proline is expensive. L-proline can be isolated and extracted from natural protein, and it is cheap and easy to get. The price ratio of D-proline and L-proline is quite different. Therefore, D-proline can be prepared from L-proline through asymmetric transformation. Proline is of great importance. Japanese Shiraiwa et al. once reported the process of preparing D-proline by asymmetric transformation method, but the consumption of raw materials and solvents is large, it is not easy to obtain pure products, and it has no practical significance in industrial production.
三、发明内容：3. Contents of the invention:
(1)发明目的(1) Purpose of the invention
本发明的目的是提供一种生产成本低、后处理容易、适合于大批量生产的一种制备D-脯氨酸的方法。The purpose of the present invention is to provide a method for preparing D-proline with low production cost, easy post-treatment and suitable for mass production.
(2)技术方案(2) Technical solution
本发明是一种制备D-脯氨酸的方法，其方法为：a、将L-脯氨酸与D-酒石酸混合并溶于有机酸中，b、加入10～30％的醛类催化剂，在80±10℃的条件下搅拌4～8小时，c、用冰水浴冷却，过滤，用无水乙醇洗涤、干燥，d、粗盐用乙醇中重结晶，得到D-酒石酸·D脯氨酸精盐，e、将D-酒石酸·D-脯氨酸精盐溶于甲醇中，f、在20～65℃的条件下，搅拌并加入氨化剂至溶液呈弱碱性，g、在室温下搅拌后，冷却至5～10℃，过滤出D-酒石酸铵盐，h、母液蒸去甲醇后，重结晶，得到D-脯氨酸。The present invention is a method for preparing D-proline. The method comprises: a. mixing L-proline and D-tartaric acid and dissolving them in organic acid; b. adding 10-30% aldehyde catalysts, Stir at 80±10°C for 4-8 hours, c, cool in an ice-water bath, filter, wash with absolute ethanol, and dry, d, recrystallize crude salt in ethanol to obtain D-tartrate·D-proline Refined salt, e. Dissolve D-tartaric acid·D-proline refined salt in methanol, f. Stir at 20-65°C and add ammoniating agent until the solution is weakly alkaline, g. Stir at room temperature Afterwards, cool to 5-10°C, filter out the ammonium salt of D-tartrate, h, evaporate methanol from the mother liquor, and then recrystallize to obtain D-proline.
D-酒石酸的回收：将酒石酸铵盐用浓硫酸中和溶解。加入丙酮或无水乙醇沉淀出硫酸铵。母液浓缩后冷却即得D-酒石酸晶体，可用于下一批次的拆分，降低了拆分剂的消耗。Recovery of D-tartaric acid: neutralize and dissolve ammonium tartrate with concentrated sulfuric acid. Add acetone or ethanol to precipitate ammonium sulfate. The mother liquor is concentrated and then cooled to obtain D-tartaric acid crystals, which can be used for the next batch of resolution, reducing the consumption of resolving agents.
(3)技术效果(3) Technical effect
本发明解决由L-型脯氨酸制备D-脯氨酸不对称转化工艺中三个主要问题。包括：The invention solves three main problems in the asymmetric conversion process of preparing D-proline from L-type proline. include:
1、溶剂消耗问题：1. Solvent consumption problem:
(1)通过拆分母液循环使用，减少了较贵重有机酸溶剂的使用量，降低了成本；(1) By splitting the mother liquor for recycling, the consumption of more expensive organic acid solvents is reduced, and the cost is reduced;
(2)粗盐后处理时，用廉价的乙醇代替易挥发、难处理、难回收的溶剂乙醚，使成本降低，操作更容易；粗盐95％乙醇中重结晶，代替原来无水乙醇和水的混合物的室温下搅拌，溶剂的用量减小、价格便宜、回收容易、母液回收95％乙醇可循环使用。(2) When crude salt is post-treated, use cheap ethanol instead of volatile, difficult to handle, and difficult to recover solvent ether, so that the cost is reduced and the operation is easier; coarse salt is recrystallized in 95% ethanol to replace the original anhydrous ethanol and water The mixture is stirred at room temperature, the amount of solvent is reduced, the price is cheap, the recovery is easy, and 95% ethanol recovered from the mother liquor can be recycled.
(3)在氨化步骤中，氨化剂改进后使氨化步骤中甲醇的用量降为原来的1/3-1/4，溶剂大大节约。因为酒石酸铵易溶于水，而难溶于甲醇等有机溶剂，如果体系中有水，必须加入较大量的甲醇，才能使酒石酸铵完全沉淀，与D-脯氨酸分开，利于产品纯化；(3) In the ammoniation step, after the ammoniation agent is improved, the amount of methanol in the ammoniation step is reduced to 1/3-1/4 of the original, and the solvent is greatly saved. Because ammonium tartrate is easily soluble in water, but insoluble in methanol and other organic solvents, if there is water in the system, a relatively large amount of methanol must be added to completely precipitate ammonium tartrate and separate it from D-proline, which is beneficial to product purification;
2、后处理问题2. Post-processing problems
(1)D-脯氨酸-D酒石酸盐固体用无水乙醇代替乙醚洗涤，洗涤效果较好，且溶剂容易处理。粗盐95％乙醇中重结晶，代替原来无水乙醇和水的混合物，溶剂的用量减小、价格便宜、回收容易。(1) The D-proline-D tartrate solid was washed with absolute ethanol instead of ether, the washing effect was better, and the solvent was easy to handle. Coarse salt is recrystallized in 95% ethanol to replace the original mixture of absolute ethanol and water, the amount of solvent used is reduced, the price is cheap, and recovery is easy.
(2)制备D-脯氨酸时，在氨化步骤中，经该改进后不会在反应体系中引入水分，使易吸水并在水中有较大溶解度的D-脯氨酸较易分离、纯化。(2) When preparing D-proline, in the ammoniation step, moisture will not be introduced in the reaction system after the improvement, so that D-proline that is easy to absorb water and has a greater solubility in water is easier to separate, purification.
3、拆分剂的回收问题3. Recycling of resolving agent
拆分剂的使用，是旋光异构体拆分过程中消耗较多，在成本中所占比例较大的一块，本发明解决了拆分剂的回收、再生问题。The use of the resolving agent consumes more in the resolution process of optical isomers and accounts for a larger proportion of the cost. The present invention solves the problem of recovery and regeneration of the resolving agent.
综上所述，本发明解决了由L-型脯氨酸制备D-脯氨酸不对称转化工艺中成本高、后处理麻烦等问题，因此，使由L-型脯氨酸制备D-脯氨酸不对称转化工艺可用于大批量工业生产。In summary, the present invention solves the problems such as high cost and troublesome post-processing in the asymmetric conversion process for preparing D-proline by L-form proline, therefore, it is possible to prepare D-proline by L-form proline The asymmetric transformation process of amino acids can be used in large-scale industrial production.
四、具体实施方式4. Specific implementation
第一步 D-酒石酸·D-脯氨酸盐制备The first step D-tartrate D-proline salt preparation
将11.5g L-脯氨酸、15.0g D-酒石酸的混合物溶于150.00mL有机酸中，加入10-30％的脂肪醛，在80±5℃下搅拌4小时，冷至室温后紧接着用冰水浴冷却0.5小时，过滤。固体用无水乙醇洗涤，干燥，得到D-脯氨酸·D-酒石酸盐的白色晶体23.1g，收率87.2％，[α]D 20 22.0°。Dissolve the mixture of 11.5g L-proline and 15.0g D-tartaric acid in 150.00mL organic acid, add 10-30% aliphatic aldehyde, stir at 80±5°C for 4 hours, cool to room temperature and then use Cool in an ice-water bath for 0.5 hour and filter. The solid was washed with absolute ethanol and dried to obtain 23.1 g of white crystals of D-proline·D-tartrate, with a yield of 87.2%, [α] D 20 22.0°.
将粗盐用95％乙醇重结晶，得19.0g精盐，收率82.3％，[α]D 20 24.0°。The crude salt was recrystallized with 95% ethanol to obtain 19.0 g of refined salt with a yield of 82.3% and [α] D 20 24.0°.
第二步 D-脯氨酸的制备The second step preparation of D-proline
将以上重结晶所得D-酒石酸·D-脯氨酸精盐26.5g溶解于甲醇中，于20-65℃及搅拌下缓慢加入氨化剂使溶液成弱碱性，在室温下搅拌1h后冷却至5～10℃，过滤并用适量甲醇洗涤固体1～2次，得D-酒石酸铵盐17.8g，收率97.0％。母液减压蒸去甲醇，并用混合溶剂重结晶，得到D-脯氨酸晶体11.0g，收率为95.6％。[α]D 20＝+84°。Dissolve 26.5 g of D-tartaric acid·D-proline refined salt obtained from the above recrystallization in methanol, slowly add an ammoniating agent under stirring at 20-65°C to make the solution weakly alkaline, stir at room temperature for 1 hour, and then cool to 5-10°C, filter and wash the solid with an appropriate amount of methanol for 1-2 times to obtain 17.8 g of D-ammonium tartrate, with a yield of 97.0%. The methanol was distilled off the mother liquor under reduced pressure, and recrystallized with a mixed solvent to obtain 11.0 g of D-proline crystals with a yield of 95.6%. [α] D 20 =+84°.
第三步 D-酒石酸的回收The third step recovery of D-tartaric acid
18.4g(0.1mol)酒石酸铵盐，用适量水湿润。在搅拌下加入浓硫酸至固体完全溶解。加入丙酮后搅拌1h。过滤，母液浓缩后冷却，得D-酒石酸晶体12.0g，收率80％。[α]D 20＝-12.0°。18.4g (0.1mol) of ammonium tartrate, moistened with appropriate amount of water. Concentrated sulfuric acid was added with stirring until the solids were completely dissolved. After adding acetone, stir for 1 h. After filtration, the mother liquor was concentrated and then cooled to obtain 12.0 g of D-tartaric acid crystals, with a yield of 80%. [α] D 20 = -12.0°.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152911A (en) * | 2015-08-17 | 2015-12-16 | 浙江邦成化工有限公司 | Recovery method of tartaric acid |
| CN106008316A (en) * | 2016-06-17 | 2016-10-12 | 成都百事兴科技实业有限公司 | New method for synthesizing Ledipasvir chiral intermediate |
| CN107827802A (en) * | 2017-10-17 | 2018-03-23 | 南京红杉生物科技有限公司 | A kind of synthetic method of D proline |
| CN112851560A (en) * | 2021-01-26 | 2021-05-28 | 南京红杉生物科技有限公司 | Preparation method of cis-D-hydroxyproline |
| CN113880802A (en) * | 2021-11-09 | 2022-01-04 | 深圳萨特瓦生物科技有限公司 | Tartaric acid-nicotine salt, preparation method and application thereof, and preparation method of anhydrous tartaric acid crystal |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105152911A (en) * | 2015-08-17 | 2015-12-16 | 浙江邦成化工有限公司 | Recovery method of tartaric acid |
| CN105152911B (en) * | 2015-08-17 | 2017-05-31 | 浙江邦成化工有限公司 | A kind of recovery method of tartaric acid |
| CN106008316A (en) * | 2016-06-17 | 2016-10-12 | 成都百事兴科技实业有限公司 | New method for synthesizing Ledipasvir chiral intermediate |
| CN107827802A (en) * | 2017-10-17 | 2018-03-23 | 南京红杉生物科技有限公司 | A kind of synthetic method of D proline |
| CN112851560A (en) * | 2021-01-26 | 2021-05-28 | 南京红杉生物科技有限公司 | Preparation method of cis-D-hydroxyproline |
| CN113880802A (en) * | 2021-11-09 | 2022-01-04 | 深圳萨特瓦生物科技有限公司 | Tartaric acid-nicotine salt, preparation method and application thereof, and preparation method of anhydrous tartaric acid crystal |
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