CN105294522A - Preparation method for D-cysteine hydrochloride monohydrate with high optical purity - Google Patents
Preparation method for D-cysteine hydrochloride monohydrate with high optical purity Download PDFInfo
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- CN105294522A CN105294522A CN201410272025.7A CN201410272025A CN105294522A CN 105294522 A CN105294522 A CN 105294522A CN 201410272025 A CN201410272025 A CN 201410272025A CN 105294522 A CN105294522 A CN 105294522A
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- 230000003287 optical effect Effects 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- QIJRTFXNRTXDIP-YBBRRFGFSA-N (2s)-2-amino-3-sulfanylpropanoic acid;hydrate;hydrochloride Chemical compound O.Cl.SC[C@@H](N)C(O)=O QIJRTFXNRTXDIP-YBBRRFGFSA-N 0.000 title abstract 3
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical compound SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 claims abstract description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 22
- 239000007789 gas Substances 0.000 claims abstract description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 14
- 239000011347 resin Substances 0.000 claims abstract description 13
- 229920005989 resin Polymers 0.000 claims abstract description 13
- 238000002425 crystallisation Methods 0.000 claims abstract description 8
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 7
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 7
- 230000008025 crystallization Effects 0.000 claims abstract description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- 239000000243 solution Substances 0.000 claims description 32
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 11
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 238000005406 washing Methods 0.000 claims description 9
- 239000007864 aqueous solution Substances 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 6
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000010521 absorption reaction Methods 0.000 claims description 5
- 230000033228 biological regulation Effects 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 5
- 230000009615 deamination Effects 0.000 claims description 4
- 238000006481 deamination reaction Methods 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims description 3
- 238000011426 transformation method Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims description 2
- 238000000746 purification Methods 0.000 abstract description 5
- 238000004821 distillation Methods 0.000 abstract description 4
- 238000005265 energy consumption Methods 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 238000012805 post-processing Methods 0.000 abstract description 3
- 239000002351 wastewater Substances 0.000 abstract description 2
- 229930195710 D‐cysteine Natural products 0.000 abstract 2
- 238000004061 bleaching Methods 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- SBIDXLKJYJVQOE-YNJMIPHHSA-M cefminox sodium Chemical class [Na+].S([C@@H]1[C@@](C(N1C=1C([O-])=O)=O)(NC(=O)CSC[C@@H](N)C(O)=O)OC)CC=1CSC1=NN=NN1C SBIDXLKJYJVQOE-YNJMIPHHSA-M 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229940124587 cephalosporin Drugs 0.000 description 2
- 150000001780 cephalosporins Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method for D-cysteine hydrochloride monohydrate with high optical purity. The method comprises steps such as D-cysteine ion exchange resin purification, hydrogen chloride gas salifying, crystallization, and the like. According to the D-cysteine ion exchange resin purification process, the 732 (H+) resin is used to play an edulcoration and concentration role, and avoids complicated post-processing steps such as distillation, bleaching, crystallization, and the like, thereby greatly reducing a technological process, lowering energy consumption, and in the premise of ensuring the optical purity of 100% in accordance with the medicine requirement, improving the yield of the D-cysteine hydrochloride monohydrate to 81% which is higher by 9% than the highest yield in current report. By means of introducing hydrogen chloride gas to salify, the amount of waste water is reduced, and the energy consumption in production is lowered, thereby avoiding disadvantages of bad color of finished products caused by a necessary high-temperature method for preparation of concentrated hydrochloric acid. Thus, the preparation method disclosed by the invention is more suitable for industrial production; and has the advantages of high yield, high quality, and being more environmentally friendly and economic.
Description
Technical field
The present invention relates to a kind of preparation method synthesizing the intermediate of third generation cephalosporin antibiotic Cefminox sodium salt, more particularly, it relates to a kind of preparation method of high optical purity D-Cys hydrochloride monohydrate.
Background technology
Halfcystine, L-type, D type or achirality DL type is all a very important seed amino acid, and D-Cys hydrochloride monohydrate is as the indispensable intermediate of synthesis third generation cephalosporin antibiotic Cefminox sodium salt, Cefminox sodium salt requires high to its optical purity.The method that the Cys that nature exists is split as D-Cys is mainly contained three kinds: 1. preferential crystallization method: this method makes to add a certain amount of left-handed or dextrorotation crystal seed in the supersaturated solution of racemic modification, then identical with crystal seed isomer is preferentially separated out.Namely adopt this method in EP009086, the D-Cys of optical purity 90% can be obtained, but yield only has 4.2%.Also use present method in US4621151, though yield is increased to 18%, optical purity only has 80%; 2. chemical resolution method: carry out chemical reaction by the reagent of optically-active and racemic modification, become diastereomer, be beneficial to different solubleness and separated.Namely US4736060 adopts this method to obtain the D-Cys of optical purity 100%, but yield is lower than 15%; 3. asymmetric transformation method: the Liu Jun of Dalian University of Technology take Cys as starting raw material, with acetone, acetic acidreaction, obtain D-Cys crude product after hydrolysis after adding tartrate, salicylic aldehyde reaction, the highest yield is 96.3%.Through 37% concentrated hydrochloric acid acidifying, after decolouring, distillation, 95% ethyl alcohol recrystallization, obtain D-Cys hydrochloride monohydrate, optical purity reaches 100%, but yield reduces to 50.5%.
Therefore, find a kind of preparation method of D-Cys hydrochloride monohydrate, make it under the prerequisite ensureing optical purity, improving its yield, is the prerequisite realizing D-Cys hydrochloride monohydrate domestic industry.
Summary of the invention
The object of the invention is to overcome above the deficiencies in the prior art, a kind of preparation method of high optical purity D-Cys hydrochloride monohydrate is provided, on aforesaid method basis 3., high optically pure D-Cys reaction solution is obtained with high yield, abandon the post-treating method that it causes low yield, find a kind of D-Cys ion-exchange resin purification, hydrogen chloride gas salify, crystallization method, not only ensure that high yield but also make its optical purity reach 100% of pharmaceutical requirements, solve the key issue realizing D-Cys domestic industry.Therefore, present invention process provides one and is more suitable for suitability for industrialized production, has the D-Cys hydrochloride monohydrate preparation method of high yield, high quality and more environmental protection and economy.
The object of the present invention is achieved like this, and the preparation process of the method comprises the following steps:
(1), with Cys and L-TARTARIC ACID for raw material, at acetone, in acetic acid or propionic acid medium, first adopt salicylic aldehyde to carry out asymmetric transformation and form D-2,2-dimethyl-thiazolidine--4-carboxylic acid-L-TARTARIC ACID salt (D-DMTL-TA);
(2), double salt through hydrolysis, obtain the D-Cys in dissolved water, adjust ph;
(3), D-Cys solution crosses 732(H
+) resin column;
(4), using ammoniacal liquor as eluent the D-Cys wash-out on resin will be adsorbed on, concentrated under elutriant vacuum condition, and make ammonia volatilization clean, obtain the aqueous solution of D-Cys;
(5), slowly pass into dry hydrogen chloride gas under cryogenic no longer to increase weight to reactant;
(6), filter after growing the grain, with after ice washing with acetone high-purity D-Cys hydrochloride monohydrate.
Concrete steps are as follows:
(1) preparation of D-2,2-dimethyl-thiazolidine--4-carboxylic acid-L-TARTARIC ACID salt (D-DMTL-TA): add Cys 242g in the reactor, L-TARTARIC ACID 300g, acetone 1000mL, acetic acid 750mL, stirring and dissolving is heated to backflow, and return time is 0.5h, and then 16mL salicylic aldehyde is added in solution, continue backflow, when reflux time is 20h, be cooled to 0 DEG C, then filter, final drying obtains D-DMTL-TA;
(2) preparation of D-Cys
The D-DMTL-TA that above-mentioned steps (1) obtains is dissolved in the distilled water of 4000mL, then after reflux 1.5h, is 2 ~ 6 by the PH of reaction solution ammoniacal liquor regulation system, namely obtains D-Cys;
(3) absorption of D-Cys and wash-out
The D-Cys aqueous solution obtained for step (2) is crossed 732 resin columns, and upper prop flow velocity is 0.5-3BV/h, washes after crossing post with the distilled water top of 100mL, and then with the ammoniacal liquor wash-out of 0.5mol/L ~ 2mol/L, finally collects elutriant;
(4) elutriant concentrates
The elutriant concentrating under reduced pressure at 50 DEG C step (3) obtained flings to ammonia, and concentrated volume 500mL, obtains deamination concentrated solution;
(5) salify
The deamination concentrated solution that step (4) obtains is cooled to-20 DEG C ~ 20 DEG C, passes into hydrogen chloride gas, period keeps temperature, no longer gains in weight, namely obtain salt to reaction solution;
(6) growing the grain
Salt step (5) obtained growing the grain 10 hours at-20 DEG C ~ 20 DEG C, then filters, then uses 0 DEG C of washing with acetone three times, dry, obtains D-Cys hydrochloride monohydrate.
The described D-Cys crude product reaction solution adjust ph 2 ~ 6 obtained with asymmetric transformation method, preferably 3.
Described solution crosses ion exchange resin column, preferably 732(H
+) resin, upper prop flow velocity is 0.5-3BV/h, preferably 1BV/h.
Described ammonia concn is 0.5mol/L ~ 2mol/L, preferably 1mol/L.
Described concentrated solution, is cooled to-20 DEG C ~ 20 DEG C, and preferable temperature is-10 ± 2 DEG C, slowly passes into dry hydrogen chloride gas.
After described reaction solution crystallization at-20 DEG C ~ 20 DEG C growing the grain 1 ~ 12h, preferably growing the grain 10h at-5 ± 2 DEG C.
The D-Cys hydrochloride monohydrate ice washing with acetone of gained.
the present invention has the following advantages and technique effect:
1, the inventive method obtains high optically pure D-Cys reaction solution with high yield, abandon the post-processing step causing low yield in prior art, find a kind of D-Cys ion-exchange resin purification, hydrogen chloride gas salify, crystallization method, not only ensure that high yield but also make its optical purity reach 100% of pharmaceutical requirements, solve the key issue realizing D-Cys domestic industry.
2, D-Cys ion-exchange resin purification process described in the inventive method adopts 732(H
+) resin, serve removal of impurities, concentrated effect, avoid complicated distillation, decolouring, crystallization, Deng post-processing step, greatly reduce technical process, reduce energy consumption, under its optical purity of guarantee reaches the prerequisite of 100% of pharmaceutical requirements, the yield of D-Cys hydrochloride monohydrate is increased to 81%, higher by 9% than the highest yield reported at present.
3, the inventive method is to pass into the mode salify of hydrogen chloride gas, decreases wastewater flow rate, reduces production energy consumption, avoids and prepares the bad drawback of finished color that necessary high temperature process brings with concentrated hydrochloric acid.Therefore, present method is more suitable for suitability for industrialized production, has the advantage of high yield, high quality and more environmental protection and economy.
Embodiment
embodiment 1
(1) preparation of D-2,2-dimethyl-thiazolidine--4-carboxylic acid-L-TARTARIC ACID salt (hereinafter referred to as D-DMTL-TA)
Cys 242g is added, L-TARTARIC ACID 300g, acetone 1000ml, acetic acid 750ml in reaction flask, stirring and dissolving be heated to backflow, backflow 0.5hr, after add 16ml salicylic aldehyde, back flow reaction 20hr, be cooled to 0 DEG C, filtration is dry afterwards obtains D-DMTL-TA615g, and this step yield is 97.6%.
(2) preparation of D-Cys and the pre-treatment of upper prop liquid
615gD-DMTL-TA is dissolved in 4000ml water, by reaction solution ammoniacal liquor regulation system PH=3 after reflux 1.5hr.
(3) absorption of D-Cys and wash-out
The D-Cys aqueous solution of about 5000mL is crossed 732 resin columns, and upper prop flow velocity is 1BV/hr, washes after crossing post with 100mL water top; With the ammoniacal liquor wash-out of 2000mL1.0mol/L, collect elutriant 2310mL.
(4) elutriant concentrates
The elutriant (3) obtained concentrating under reduced pressure at 50 DEG C flings to ammonia, and concentrated volume is to 500mL.
(5) salify
The concentrated solution that (4) obtain is cooled to-5 DEG C, passes into hydrogen chloride gas, period keeps temperature to be-5 DEG C ~ 0 DEG C, no longer gains in weight, increase weight as 189g to reaction solution.
(6) growing the grain
Growing the grain 10 hours at-5 DEG C, filters, with ice washing with acetone three times, dry, obtains D-Cys hydrochloride monohydrate 284.3g, total recovery 81%, optical purity 100%, chemical purity 99.6%.
embodiment 2
(1) with executing (1) in example 1
(2) preparation of D-Cys and the pre-treatment of upper prop liquid
615gD-DMTL-TA is dissolved in 4000ml water, by reaction solution ammoniacal liquor regulation system PH=5 after reflux 1.5hr.
(3) absorption of D-Cys and wash-out
The D-Cys aqueous solution of about 5000mL is crossed 732 resin columns, and upper prop flow velocity is 1BV/hr, washes after crossing post with 100mL water top; With the ammoniacal liquor wash-out of 2000mL1.5mol/L, collect elutriant 2280mL.
(4) elutriant concentrates
The elutriant (3) obtained concentrating under reduced pressure at 50 DEG C flings to ammonia, and concentrated volume is to 500mL.
(5) salify
The concentrated solution that (4) obtain is cooled to-5 DEG C, passes into hydrogen chloride gas, period keeps temperature to be-5 DEG C ~ 0 DEG C, no longer gains in weight, increase weight as 185.4g to reaction solution.
(6) growing the grain
Growing the grain 5 hours at-5 DEG C, filters, with ice washing with acetone three times, dry, obtains D-Cys hydrochloride monohydrate 254.5g, total recovery 72.5%, optical purity 100%, chemical purity 99.7%.
embodiment 3
(1) with (1) in embodiment 1
(2) with (2) in embodiment 1
(3) absorption of D-Cys and wash-out
The D-Cys aqueous solution of about 5000mL is crossed WA-2 resin column, and upper prop flow velocity is 1BV/hr, washes after crossing post with 100mL water top; With the ammoniacal liquor wash-out of 2000mL1.5mol/L, collect elutriant 2120mL.
(4) elutriant concentrates
The elutriant (3) obtained concentrating under reduced pressure at 50 DEG C flings to ammonia, and concentrated volume is to 500mL.
(5) salify
The concentrated solution that (4) obtain is cooled to-5 DEG C, passes into hydrogen chloride gas, period keeps temperature to be-5 DEG C ~ 0 DEG C, no longer gains in weight, increase weight as 176g to reaction solution.
(6) growing the grain
Growing the grain 5 hours at-5 DEG C, filters, with ice washing with acetone three times, dry, obtains D-Cys hydrochloride monohydrate 179g, total recovery 51%, optical purity 100%, chemical purity 98.7%.
embodiment 4
(1) with (1) in embodiment 1
(2) preparation of D-Cys:
615gD-DMTL-TA is dissolved in 4000ml water, reflux 1.5h, after reaction solution is concentrated into about 400ml, with 275ml triethylamine regulation system PH=3.6, then add 2100ml ethanol, stir and within 10 minutes, be cooled to 20 DEG C of filtrations, drying, obtains D-Cys 340g.
(3) synthesis of D-Cys hydrochloride monohydrate:
D-Cys 340g is dissolved in the mixed solution of 600ml water and 350ml concentrated hydrochloric acid composition, at 80 DEG C, stirring reaction is after 30 minutes, add 25g gac, continue stirring 10 minutes, cross and filter gac, underpressure distillation remains about 400ml after anhydrating, leave standstill and be cooled to about-5 DEG C, filtered by the crystal of the white separated out, ice acetone is washed, dry that D-Cys hydrochloride monohydrate is about 253g.Optical purity 100%, chemical purity 99.23%, yield 72%.
Claims (8)
1. a preparation method for high optical purity D-Cys hydrochloride monohydrate, is characterized in that: the step of the method is as follows:
(1), with Cys and L-TARTARIC ACID for raw material, at acetone, in acetic acid or propionic acid medium, first adopt salicylic aldehyde to carry out asymmetric transformation and form D-2,2-dimethyl-thiazolidine--4-carboxylic acid-L-TARTARIC ACID salt (D-DMTL-TA);
(2), double salt through hydrolysis, obtain the D-Cys in dissolved water, adjust ph;
(3), D-Cys solution crosses 732(H
+) resin column;
(4), using ammoniacal liquor as eluent the D-Cys wash-out on resin will be adsorbed on, concentrated under elutriant vacuum condition, and make ammonia volatilization clean, obtain the aqueous solution of D-Cys;
(5), slowly pass into dry hydrogen chloride gas under cryogenic no longer to increase weight to reactant;
(6), filter after growing the grain, with after washing with acetone high-purity D-Cys hydrochloride monohydrate.
2. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate according to claim 1, is characterized in that:
The concrete steps of the method are as follows:
(1) preparation of D-2,2-dimethyl-thiazolidine--4-carboxylic acid-L-TARTARIC ACID salt (D-DMTL-TA): add Cys 242g in the reactor, L-TARTARIC ACID 300g, acetone 1000mL, acetic acid 750mL, stirring and dissolving is heated to backflow, and return time is 0.5h, and then 16mL salicylic aldehyde is added in solution, continue backflow, when reflux time is 20h, be cooled to 0 DEG C, then filter, final drying obtains D-DMTL-TA;
(2) preparation of D-Cys
The D-DMTL-TA that above-mentioned steps (1) obtains is dissolved in the distilled water of 4000mL, then after reflux 1.5h, is 2 ~ 6 by the PH of reaction solution ammoniacal liquor regulation system, namely obtains D-Cys;
(3) absorption of D-Cys and wash-out
The D-Cys aqueous solution obtained for step (2) is crossed 732 resin columns, and upper prop flow velocity is 0.5-3BV/h, washes after crossing post with the distilled water top of 100mL, and then with the ammoniacal liquor wash-out of 0.5mol/L ~ 2mol/L, finally collects elutriant;
(4) elutriant concentrates
The elutriant concentrating under reduced pressure at 50 DEG C step (3) obtained flings to ammonia, and concentrated volume 500mL, obtains deamination concentrated solution;
(5) salify
The deamination concentrated solution that step (4) obtains is cooled to-20 DEG C ~ 20 DEG C, passes into hydrogen chloride gas, period keeps temperature, no longer gains in weight, namely obtain salt to reaction solution;
(6) growing the grain
Salt step (5) obtained growing the grain 10 hours at-20 DEG C ~ 20 DEG C, then filters, then uses 0 DEG C of washing with acetone three times, dry, obtains D-Cys hydrochloride monohydrate.
3. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, is characterized in that: the D-Cys crude product reaction solution that step (2) obtains with asymmetric transformation method regulates preferably 3.
4. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, is characterized in that: the solution described in step (3) crosses ion exchange resin column, preferably 732(H
+) resin, upper prop flow velocity preferably 1BV/h.
5. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, is characterized in that: the ammonia concn preferably 1mol/L described in step (3).
6. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, it is characterized in that: the concentrated solution described in step (5), preferable temperature is-10 ± 2 DEG C, slowly passes into dry hydrogen chloride gas.
7. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, is characterized in that: at lower growing the grain 1 ~ 12hr after the reaction solution crystallization described in step (6), growing the grain 10hr at preferred-5 ± 2 DEG C.
8. the preparation method of a kind of high optical purity D-Cys hydrochloride monohydrate as claimed in claim 2, is characterized in that: D-Cys hydrochloride monohydrate 0 DEG C of washing with acetone of step (6) gained.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108715586A (en) * | 2018-06-27 | 2018-10-30 | 湖北远大生物技术有限公司 | A kind of reuse method of enzymatic reaction l-cysteine mother liquor |
| CN114149350A (en) * | 2021-12-15 | 2022-03-08 | 上虞新和成生物化工有限公司 | Method for extracting cysteine or salt thereof from reaction liquid and application thereof |
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| US4374247A (en) * | 1979-12-07 | 1983-02-15 | Sogo Pharmaceutical Co., Ltd. | Process for preparing 2,2-disubstituted thiazolidines |
| CN101245042A (en) * | 2007-02-14 | 2008-08-20 | 瓦克化学股份公司 | Process for purifying L-cysteine |
| CN102234244A (en) * | 2010-04-22 | 2011-11-09 | 四平市精细化学品有限公司 | D-cysteine hydrochloride monohydrate preparation method |
| CN103476748A (en) * | 2011-04-20 | 2013-12-25 | 瓦克化学股份公司 | Method for purifying L-cysteine |
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2014
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| CN114149350A (en) * | 2021-12-15 | 2022-03-08 | 上虞新和成生物化工有限公司 | Method for extracting cysteine or salt thereof from reaction liquid and application thereof |
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