CS271251B1 - Cleaning and insulating method for sodium salt cellophatine - Google Patents
Cleaning and insulating method for sodium salt cellophatine Download PDFInfo
- Publication number
- CS271251B1 CS271251B1 CS856795A CS679585A CS271251B1 CS 271251 B1 CS271251 B1 CS 271251B1 CS 856795 A CS856795 A CS 856795A CS 679585 A CS679585 A CS 679585A CS 271251 B1 CS271251 B1 CS 271251B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- sodium
- thienylacetamido
- acid
- acetate
- sodium salt
- Prior art date
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- 159000000000 sodium salts Chemical class 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 title claims description 10
- 238000004140 cleaning Methods 0.000 title abstract 2
- 229960000603 cefalotin Drugs 0.000 claims abstract description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 16
- -1 alkyl acetate Chemical compound 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 11
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 239000011780 sodium chloride Substances 0.000 claims abstract description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 7
- 239000001632 sodium acetate Substances 0.000 claims abstract description 7
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 7
- 238000000605 extraction Methods 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000002955 isolation Methods 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract 2
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 claims description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 12
- 239000011734 sodium Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 239000000243 solution Substances 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 238000000746 purification Methods 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 3
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 abstract 2
- 229930186147 Cephalosporin Natural products 0.000 abstract 1
- 229940124587 cephalosporin Drugs 0.000 abstract 1
- 238000002347 injection Methods 0.000 abstract 1
- 239000007924 injection Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Cephalosporin Compounds (AREA)
Abstract
Description
Vynález sa týká ekonomizác-e výroby velmi čistej sodnej soli cefalotínu/sodnej soli 7-/2-tienylacetamido/-cefalosporánovej kyseliny/, substancie pře výrobu injekčnej formy tohoto ši rokosрекtгá1neho antibiotika.The invention relates to the economization of the production of a very pure cephalotin sodium salt of 7- (2-thienylacetamido) -cephalosporanoic acid sodium, a substance for the preparation of an injectable form of this broad-spectrum antibiotic.
Problém čistenia cefalotínových solí bol v nedávnej době zásadné riešený AO č. 225 196, podl’a ktorého sa sodná sol cefalotínu s čistotou 90-93 % a absorbanciou Ρθά θι3 v dobrom výtažku izoluje zo znečistenej reakčnej masy obsahujúcej kyselinu 7-/2-tieny1acetamido/-cefalosporánovú, jej sodnú sol extrakciou kyseliny 7-/2-tienylácetamido/-cefalosporánovej do octanu alkylového po okyselení reakčnej masy na pH = 1 až 2 a extrakciou octanového extraktu vodným roztokom octanu sodného, z ktorého sa izolovala sodná sol cefalo- 4 tínu chloridom sodným v kryštalickej formě.The problem of purification of cephalotin salts has recently been solved fundamentally by AO no. 225 196, according to which cephalotin sodium with a purity of 90-93% and an absorbance of Ρθά θ 3 in good yield is isolated from a contaminated reaction mass containing 7- (2-thienylacetamido) -cephalosporanic acid, its sodium salt by extraction of 7- (7) 2-thienylacetamido / -cephalosporanoic acid into alkyl acetate after acidifying the reaction mass to pH = 1-2 and extracting the acetate extract with an aqueous solution of sodium acetate from which cephalitin sodium salt was isolated in sodium form in crystalline form.
Hoci je metoda čistenia alebo izolácie jednoduchá a dosahuje poměrně vysoký výťažok i * čistotu produktu, nie sú to hodnoty optimálně. Na závadu je obsah chloridov v produkte do 3 % hmot.Although the purification or isolation method is simple and achieves a relatively high yield and purity of the product, these are not optimal. The content of chlorides in the product is up to 3% by weight.
Postupom podlá vynálezu qa podařilo spojit operáciu extrakcie roztoku octanu sodného a vysolovanie chloridom sodným v jediná operáciu, ktorá vedie к vyššej čistotě i výtažku sodnej soli cefalotínu.According to the process of the invention, qa has been able to combine the operation of extraction of the sodium acetate solution and salting out with sodium chloride in a single operation which leads to higher purity and yield of cephalotin sodium.
Podstata spósobu podlá vynálezu spočívá v okyselení vodných roztokov kyseliny 7-/2-tienylacetamido/-cefalosporánovej získaných okyselením reakčnej masy obsahujúcej sodnú alebo trietylamóniovú sol’ cefalotínu, připadne i s volným cefalotínom, silnou minerálnou kyselinou na pH = 1 až 2 a extrakciou kyslého roztoku octanom alkylnatým s počtom uhlíkov 2 až 4 v alkyle a případným přečištěním octanového roztoku aktívným uhlím vyznačená tým, 2e sa к organickému extraktu přidá vodný roztok octanu sodného v množstve 1 až 1,4 ekvivalentu a chloridu sodného v množstve 4,5 až 7,45 ekvivalentu na ekvivalent kyseliny 7-/2-tieny1acetamido/-cefalosporánovej kyseliny při celkovej koncentrácii vodného roztoku solí 17 až 26 % hmot., při teplotách 15 až 25 °C a za 30 minut až 3 hodiny vykrystalizovaná čistá sodná sol cefalotínu sa izoluje známým postupom.The process according to the invention consists in acidifying aqueous solutions of 7- (2-thienylacetamido) -cephalosporanoic acid obtained by acidifying the reaction mass containing the cephalotin sodium or triethylammonium salt, optionally with free cephalotin, a strong mineral acid to pH = 1 to 2 and extraction with acidic acid. (2e) an aqueous solution of sodium acetate in an amount of 1 to 1.4 equivalents and sodium chloride in an amount of 4.5 to 7.45 equivalents is added to the organic extract to an organic extract; to the equivalent of 7- (2-thienylacetamido) -cephalosporanoic acid at a total aqueous salt solution concentration of 17-26% by weight, at temperatures of 15-25 ° C and after 30 minutes to 3 hours, crystallized pure cephalotin sodium is isolated by a known method.
Výhodou postupu podlá vynálezu je univerzálnost metody, ktorá dovoluje spracovať aj znečistěné trietylamóniovej soli cefalotínu na sodnú sol cefalotínu vysokej čistoty.An advantage of the process according to the invention is the versatility of the method, which also permits the treatment of impure triethylammonium salts of cephalotin into high purity cephalotin sodium.
Postup podlá vynálezu demonštrujú příklady prevedenia.The process according to the invention is illustrated by exemplary embodiments.
Příklad č. 1Example # 1
Ku 120 ml reakčnej zmesi obsahujúcej 13 až 15 g sodnej soli cefalotinu/resp. 15,5 až 17,8 g trietylamóniovej soli cefalotínu/, 7 g trietylamí nu, 1,7 g chloridu sodného, 4,9 g kyseliny pivalovej, 0,5 g kyseliny tiofenoctovej, asi 2,5 g neidentifikovaných rozkladných produktov a nečistót z východzích surovin a 80 ml vody sa přidá 200 ml octanu etylového vlhkého. Za premiešáváni a sa vodný roztok okyselí zriedenou kyselinou chlorovodíkovou na pH 1,5 až 1. Po okyselení sa zmes mieša 30 minút a nechá sa v kl’ude 40 až 60 minut. Spodná vodná vrstva sa ešte raz extrahuje 30 až 100 ml octanu etylového a po oddělení extraktu sa organické vrstvy spoja, premyjú 3 krát po 100 ml vody do neutrálnej reakcie. Etylacetátový roztok sa premiešá.s 1,8 g karborafínu a přefiltruje sa. ·To 120 ml of a reaction mixture containing 13-15 g of cephalotin sodium / resp. 15.5 to 17.8 g of cephalotin triethylamine salt, 7 g of triethylamine, 1.7 g of sodium chloride, 4.9 g of pivalic acid, 0.5 g of thiopheneacetic acid, about 2.5 g of unidentified decomposition products and impurities from starting material and 80 ml of water were added 200 ml of ethyl acetate. While stirring, the aqueous solution is acidified with dilute hydrochloric acid to pH 1.5 to 1. After acidification, the mixture is stirred for 30 minutes and left to rest for 40 to 60 minutes. The lower aqueous layer is extracted once more with 30 to 100 ml of ethyl acetate and, after separation of the extract, the organic layers are combined, washed 3 times with 100 ml of water until neutral. The ethyl acetate solution is stirred with 1.8 g of carboraffin and filtered. ·
К filtrátu se přidá roztok 60 ml vody, 6 g octanu sodného kryšta 1 ického a 18 g chlori du sodného a zmes sa mieša. Už po 30 minutách zo zmesi vykrystalizuje sodná sol’ cefalotínu .A solution of 60 ml of water, 6 g of crystalline sodium acetate and 18 g of sodium chloride is added to the filtrate and the mixture is stirred. After 30 minutes, the cephalotin sodium crystallizes out of the mixture.
Po 2 hodinách sa kryštalický produkt oddělí na centrifúge premvje 50 až 100 ml acetonu. Po vysušení sa získá 12,5 až 14,5 g sodnej soli cefalotínu s obsahom 95 až 98 % stanovenu metodou kvapalinovej chromátografie a s absorbanciou pri pod 0,2. Obsah chloridu sodného sa pohybuje od 0,05 do 0,17 %. Výťažok čistenia je 96 % teorie.After 2 hours, the crystalline product is collected on a centrifuge and washed with 50 to 100 ml of acetone. After drying, 12.5 to 14.5 g of cephalotin sodium are obtained with a content of 95 to 98% as determined by liquid chromatography and an absorbance at below 0.2. The sodium chloride content ranges from 0.05 to 0.17%. The purification yield is 96% of theory.
CS 271251 BlCS 271251 Bl
Příklad č.2 /Example 2 /
Postupuje sa ako v příklade č. 1, avšak к octanovému filtrátu sa přidá roztok 60 ml vody, 13 g chloridu sodného a 6 q krystalického octanu sodného a ďalej sa opáť postupuje podlá příkladu č. 1. Získá sa 11,5 až 12 g sodnej soli cefalotínu. Absorbancia Α^θθ * 0,1 až 0,15 a obsah 97 až 99 %.The procedure is as in example no. 1, but a solution of 60 ml of water, 13 g of sodium chloride and 6 g of crystalline sodium acetate is added to the acetate filtrate, and the procedure of Example 1 is repeated. 1. 11.5-12 g of cephalotin sodium are obtained. Absorbance Α ^ θθ * 0.1 to 0.15 and 97 to 99% content.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS856795A CS271251B1 (en) | 1985-09-24 | 1985-09-24 | Cleaning and insulating method for sodium salt cellophatine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS856795A CS271251B1 (en) | 1985-09-24 | 1985-09-24 | Cleaning and insulating method for sodium salt cellophatine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS679585A1 CS679585A1 (en) | 1987-08-13 |
| CS271251B1 true CS271251B1 (en) | 1990-09-12 |
Family
ID=5415809
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS856795A CS271251B1 (en) | 1985-09-24 | 1985-09-24 | Cleaning and insulating method for sodium salt cellophatine |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS271251B1 (en) |
-
1985
- 1985-09-24 CS CS856795A patent/CS271251B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS679585A1 (en) | 1987-08-13 |
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