CS259381B1 - Method of 1h-1-tetrazolylacetic acid's chloride preparation - Google Patents
Method of 1h-1-tetrazolylacetic acid's chloride preparation Download PDFInfo
- Publication number
- CS259381B1 CS259381B1 CS863232A CS323286A CS259381B1 CS 259381 B1 CS259381 B1 CS 259381B1 CS 863232 A CS863232 A CS 863232A CS 323286 A CS323286 A CS 323286A CS 259381 B1 CS259381 B1 CS 259381B1
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- reaction
- chloride
- acetic acid
- formula
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 title claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 239000012429 reaction media Substances 0.000 claims abstract description 9
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims abstract 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 18
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 11
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims description 8
- -1 1H-1-tetrazolyl acetic acid chloride Chemical compound 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims 1
- 230000008020 evaporation Effects 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- 230000035484 reaction time Effects 0.000 claims 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 abstract description 4
- 229930186147 Cephalosporin Natural products 0.000 abstract description 3
- 229940124587 cephalosporin Drugs 0.000 abstract description 3
- 150000001780 cephalosporins Chemical class 0.000 abstract description 3
- 239000003242 anti bacterial agent Substances 0.000 abstract description 2
- 229940088710 antibiotic agent Drugs 0.000 abstract description 2
- RCJVRSBWZCNNQT-UHFFFAOYSA-N dichloridooxygen Chemical compound ClOCl RCJVRSBWZCNNQT-UHFFFAOYSA-N 0.000 abstract description 2
- 230000000844 anti-bacterial effect Effects 0.000 abstract 1
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- GRWAIJBHBCCLGS-UHFFFAOYSA-N 2-(tetrazol-1-yl)acetic acid Chemical compound OC(=O)CN1C=NN=N1 GRWAIJBHBCCLGS-UHFFFAOYSA-N 0.000 description 1
- HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical class S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
Abstract
Riešenie sa týká přípravy chloridu kyseliny ΙΗ-1-tetrazolyloctovej, ktorý slúži na přípravu polosyntetických cefalosporínových antibiotik s antibakteriálnou účinnosťou. Sposob přípravy je založený na reakcii kyseliny lH-l-teířazOOlyloetOVéj s Chloridom fosforečným v prostředí oxychloridu fosforečného, alebo bez reakčného prostredia.The solution relates to the preparation of an acid chloride ΙΗ-1-tetrazolyl acetic acid, which is used in the preparation of semi-synthetic cephalosporins antibiotics with antibacterial activity. The method of preparation is based on the reaction with 1 H-1-thiocarboxylic acid with chloride phosphorous in oxychloride phosphorous or without the reaction medium.
Description
2S9381
Vynález sa týká sposobu přípravy chlori-du kyseliny lH-l-tetrazolylocotovej vzorcaI 74108 091 (1974); Ger. Offen 2 540 374(1975); Ger. Offen 2 730 579 (1976)] týka-júcich sa přípravy polosyntetických cefa-losporínových antibiotik s lH-l-tetrazolyl-acetamidovým zoskupením v polohe C7-ce-fémového skeletu, ale ani v jednom patentenie je sposob přípravy zlúčeniny vzorca Ipopísaný. V týchto patentoch sa lH-l-tetrazolyla-cetylchlorid uvádza ako hotová zlúčeninabez uvedeného sposobu přípravy a fyzikál-no-chemických vlastností (teplota topenia,elementárna analýza, IČ spektrum a podob-né).
Sposob přípravy zlúčeniny vzorca I podlávynálezu je založený na reakcii ΙΗ-1-tetra-zolyloctovej kyseliny vzorca III
Zlúčenina vzorca I sa používá na přípra-vu 7-[lH-tetrazol-l-yl-acetamido ]-3-[ (5--metyl-l,3,4-tiadiazol-2-yl) -tiometyl ] -3-ce-fém-4-karboxylovej kyseliny vzorca II
c c Ň- (4. (II)
o (///.? ktorá slúži ako, polosyntetické cefalosporí-nové antibiotikum so širokým spektrom ú-činku proti gram-pozitívnym a gram-nega-tívnym baktériám (viz AO č. 242 274). lH-l-Tetrazoolylacetylchlorid sa uvádzaako reakčné činidlo vo viacerých patentoch[viz napr. Ger. Offen 2 263 861 (1972); Ger.Offen 2 318 829 (1973); Japan Kokai s chloridom fosforečným a) bez reakčného prostredia, alebo b) v prostředí oxychloridu fosforečného. Přítomnost oxychloridu fosforečného, akoreakčného prostredia je v reagujúcej zme-si závislé od molárneho množstva reagujú-cich látok (kyseliny lH-l-tetrazolyloctoveja chloridu fosforečného). Oxychlorid fosfo-rečný plní funkciu reakčného prostredia(média), ktoré umožňuje lepšie zvládnut e- 259381 5 xotermický priebeh reakcie při vačších mo-lárnych navážkách.
Keď množstvo reagujúcich látok nepře-vyšuje 0,1 molu, tak exotermický priebeh re-akcie nie je vel'mi prudký. Teplota vystúpimaximálně na 60 °C a v tomto případe pro-stredie POCf, nie je nutné na umožnenielepšielio přestupu tepla pri chladení reagu-júcej zmesi.
Pri molárnych množstvách kyseliny 1H-1--tetrazolyloctovej a chloridu fosforečnéhonad 0,1 molu je exotermický priebeh reak-cie velmi intenzívny a reagujúca zmes samusí chladit. Teplota reakčnej zmesi nesmieprestúpiť 60 °C, pretože nad touto teplotousa vznikajúci chlorid kyseliny ΙΗ-1-tetra-zolyloctovej rozkládá, čo sa prejaví v zní-žení výťažkov. Na lepšie sprostredkovaniepřestupu tepla a zároveň mierne potlačeniekinetiky reakcie vhodné slúži oxychloridfosforečný ako reakčné prostredie v opti-málnom štvormolárnom nadbytku voči ky-selme IH-l-tetrazolyloctovej.
Pri spósobe přípravy zlúčeniny vzorca Ibez reakčného prostredia sa vysušená 1H-Í--tetrazolyloctová kyselina naraz zmieša sekvimolárnym množstvom chloridu fosfo-rečného a po búrlivom exotermickom prie-behu reakcie sa skvapalnená zmes ešte po-noří do temperovaného kúpefa vyhriatehona 55 °C. Po oddestilovaní uvolněného oxy-chloridu fosforečného zo zreagovanéhochloridu fosforečného sa olejovitý zbytekvymrazí a tuhý surový chlorid sa za stude-ná extrahuje do! dichlórmetánu, čím sa jed-noducho oddělí případná nezreagovaná ky-octovej a po odkvapkaní sa sušia 21 hodinselina ΙΗ-1-tetrazolyloctová, ktorá je vchlórmetánu pri použití vodného kúpefa vy-hriateho maximálně na 30 °C dojde k silné-mu podchladeniu rozpúšťadla, čím sprievod-ne dochádza ku kryštalizácii zlúčeniny vzor-ca I podlá vynálezu.
Sposob izolácie zlúčeniny vzorca I podfavynálezu pripravenej v prostředí oxychlori-du fosforečného je analogický ako v pred-chádzajúcom případe. Rozdiel je len v tom,že z reakčnej zmesi třeba oddestilovať vač-šie množstvo oxychloridu fosforečného. Výhodou postupu podfa vynálezu je spo-íahlivá reprodukovatefnosť vysokých výťaž-kov chloridu kyseliny lH-l-tetrazolylocto-vej. Takto připravený kryštalický svetložl-tý chlorid kyseliny IH-l-tetrazolyloctovej jestabilný a može sa ďalej použiť na N-acy-lačnú reakciu s derivátmi 7-amínocefalospo-ránovej kyseliny bez ďalšieho prečistenia. Příklad 1 V 250 ml jednohrdlej banke sa narazzmieša 12,8 g (0,1 molu) kyseliny ΙΗ-1-te-trazolyloctovej s 21,08 g 0,101 mólu) chlo-ridu fosforečného, banka sa uzavře chlór-kalciovým uzáverom. Počas jednej minútysa zmes roztopí, zároveň sa uvolní odpove-dajúce množstvo chlorovodíka a roztopená zmes dosiahne teplotu 48 °C. Keď teplotazačne volné klesat, banka s reakčnou zme-sou sa ponoří do kúpefa temperovaného na55 °C a zvyšok kyseliny v podobě drobnýchkryštalických hrudiek sa nechá v priebehu5 minút doreagovať. Vzniknutý červený roz-tok sa odpaří do sucha behom 15 minút priteplote kúpefa maximálně 55 °C a olejovi-tý zbytok sa vymrazením a třením skleně-nou tyčinkou nechá vykrystalizovat Suro-vý tuhý chlorid kyseliny ΙΗ-1-tetrazolyloc-tovej sa extrahuje za studená do 200 mldichlórmetánu, extrakt sa premieša s ak-tívnym uhlím, přefiltruje sa a odpaří sa naodparke do sucha bez použitia vodného kú-pefa, alebo pri teplote kúpefa 30 °C. Tým sadosiahne silné podchladenie obsahu bankya chlorid kyseliny IH-l-tetrazolyloctovejkryštalizuje z roztoku v podobě žitých kryš-tálov. Získá sa 14 g (95,2 %) zlúčeniny vzor-ca I, teplota topenia 59—60 °C (dichlórme-tán). Příklad 2
Do jednolitrovej trojhrdlej banky s mie-šadlom, teplomerom a přídavným lievikomsa nasype 128,09 (1 mól) kyseliny IH-l-te-trazolyloctovej a vzápatí sa naraz prileje 367,2 ml (4 moly) oxychloridu fosforečné-ho. Počas miešania sa do reakčnej zmesipostupné prisypáva 210,8 g (1,01 mólu)chloridu fosforečného tak, aby teplota re-akčnej zmesi neprestúpila 55 °C. Reakčnúzmes je preto třeba chladit vodným kúpe-l'om. Po přidaní chloridu fosforečného sazbytok kyseliny nechá ešte doreagovať vpriebehu 5 minút pri teplote kúpefa 55 °C.Vzniknutý číry červený roztok sa potom pre-leje do jednolitrovej banky a oxychloridfosforečný sa odpaří do sucha pri teplotekúpefa maximálně 55 °C. Olejovitý červenýzbytok sa vymrazí a třením skleněnou ty-činkou vykrystalizuje. Surový žitý chloridkyseliny IH-l-tetrazolyloctovej sa extrahu-je za studená 3 x 650 ml dichlórmetánu, ex-trakt sa premieša s aktívnym uhlím, pře-filtruje sa a odpaří sa na odparke pri tep-lote kúpefa 30 °C. Tým sa dosiahne silnépodchladenie obsahu banky a chlorid vy-krystalizuje v podobě žitých kryštálov. Zís-ká sa 131,89 až 140 g (90 až 95,2 %) zlúče-niny vzorca I, teplota topenia 59 až 60 °C(dichlórmetán). Pře C3H3N4OC1 (m. h. 146,55 g.mól-1).Vypočítané: 24,56 % C, 2,04 % H, 38,36 θ/ο N, 24,20 % Cl,Stanovené: 24,44 % C, 2,00 % H, 38,56 % N, 24,59 % Cl. IČ spektrum zlúčeniny vzorca I podfa vy- nálezu v chloroforme má charakteristický pás karbonylovej skupiny pri 1799 cm'1.
2S9381
The present invention relates to a process for the preparation of the acid chloride of 1H-1-tetrazolylocote of formula I 74108 091 (1974); Ger. Offen 2,540,374 (1975); Ger. Offen 2 730 579 (1976)] for the preparation of semisynthetic cephalosporin antibiotics with 1 H-1-tetrazolyl acetamide moiety at the C 7 -cell skeleton position, but not in one patent is a method for the preparation of the compound of formula I described. In these patents, 1H-1-tetrazolylacetic chloride is disclosed as a ready-to-use compound and physical-chemical properties (melting point, elemental analysis, IR spectrum and the like).
The process for preparing the compound of formula I according to the invention is based on the reaction of ΙΗ-1-tetra-zolyl acetic acid of formula III
The compound of formula I is used to prepare 7- [1H-tetrazol-1-yl-acetamido] -3 - [(5-methyl-1,3,4-thiadiazol-2-yl) -thiomethyl] -3- the cis-4-carboxylic acid of formula II
cc Ň- (4 (II))
o (which serves as a semi-synthetic cephalosporin antibiotic with a broad spectrum of action against gram-positive and gram-negative bacteria (see AO No. 242,274). an agent in several patents [see, e.g., Ger. Offen 2 263 861 (1972); Ger.Offen 2 318 829 (1973); Japan Kokai with phosphorus pentachloride a) without reaction medium; or b) phosphorus oxychloride. The presence of phosphorous oxychloride and the reaction medium is dependent on the molar amount of reactants (1H-1-tetrazolyl acetic acid and phosphorus pentachloride) in the reaction medium. Phosphoric oxychloride functions as a reaction medium (medium) that allows the e-259381 5-hour reaction to be better controlled at larger molecular weights.
When the amount of reactants does not exceed 0.1 mole, the exothermic course of the re-action is not very rapid. The temperature reaches a maximum of 60 ° C, and in this case the POCF, it is not necessary to allow the heat transfer to cool over the reacting mixture.
At molar amounts of 1H-1-tetrazolylacetic acid and 0.1 mole of phosphoric acid chloride, the exothermic course of the reaction is very intense and the reacting mixture must be cooled. The temperature of the reaction mixture must not exceed 60 ° C, since the β-1-tetrazolylic acid chloride formed above this temperature decomposes, resulting in reduced yields. For better heat transfer and at the same time mild suppression of the reaction kinetics, phosphorus oxychloride is suitable as the reaction medium in an optimum four-molar excess over 1H-1-tetrazolyl acetic acid.
To prepare the compound of formula (Ib) from the reaction medium, the dried 1H-tetrazolyl acetic acid is mixed together with a sequential amount of phosphorous chloride and, after a vigorous exothermic reaction, the liquefied mixture is immersed in a tempered bath heated to 55 ° C. After distilling off the phosphorus oxychloride liberated from the reacted phosphorous chloride, the oily residue was frozen and the solid crude chloride was extracted into the cold residue. Dichloromethane, whereupon the optional unreacted acetic acid is separated off and, after the dripping, 21-β-1-tetrazolyl acetic acid, which is in chloromethane, is dried using a water bath heated to max. accompanying crystallization of the compound of formula I according to the invention.
The method of isolating the compound of formula I prepared in the phosphorus oxychloride medium is analogous to the previous case. The only difference is that more phosphorus oxychloride needs to be distilled off the reaction mixture. An advantage of the process of the invention is the reliable reproducibility of high yields of 1H-1-tetrazolyl acetic acid chloride. The thus prepared crystalline light l'H-1-tetrazolylacetic acid chloride is stable and can be further used for the N-acylation reaction with 7-aminocephalosporanic acid derivatives without further purification. EXAMPLE 1 12.8 g (0.1 mole) of β-1-tetrazolyl acetic acid with 21.08 g of 0.101 mole of phosphorus pentachloride are mixed in a 250 ml single neck flask and the flask is sealed with a chloro-cap. During one minute, the mixture melts, while the corresponding amount of hydrogen chloride is released and the melted mixture reaches a temperature of 48 ° C. When the temperature drops freely, the flask with the reaction mixture is immersed in a bath heated to 55 ° C and the acid residue in the form of small crystalline lumps is allowed to react within 5 minutes. The resulting red solution is evaporated to dryness within 15 minutes and the bath is allowed to warm to a maximum of 55 ° C and the oily residue is crystallized and rubbed with a glass rod. The crude β-1-tetrazolylic acid chloride is extracted cold up to 200 billion dichloromethane, the extract is mixed with activated charcoal, filtered and evaporated to dryness without the use of an aqueous solvent, or at a bath temperature of 30 ° C. Thereby, a strong undercooling of the contents of the flask and the IH-1-tetrazolylacetic acid chloride crystallize from the solution in the form of rye crystals. 14 g (95.2%) of the compound of formula (I) are obtained, m.p. 59-60 ° C (dichloromethane). Example 2
Pour 128.09 (1 mol) of 1 H-1-tertrazolylacetic acid into a one-liter three-necked flask with a stirrer, thermometer and additional funnel and then add 367.2 ml (4 mol) of phosphorous oxychloride in one portion. While stirring, 210.8 g (1.01 mol) of phosphorus pentachloride are poured into the reaction mixture so that the temperature of the reaction mixture does not exceed 55 ° C. The reaction mixture should therefore be cooled with an aqueous bath. After the addition of phosphorus pentachloride, the acid is left to react for 5 minutes at 55 ° C. The clear red solution is then poured into a 1 liter flask and the phosphorus oxychloride is evaporated to dryness at a maximum temperature of 55 ° C. The oily red residue is frozen and crystallized by friction with a glass rod. The crude IH-1-tetrazolylacetic acid chloride chloride was extracted with cold 3 x 650 ml of dichloromethane, the extract was mixed with activated carbon, filtered and evaporated in an evaporator at a bath temperature of 30 ° C. This achieves a strong cooling of the contents of the flask and the chloride crystallizes in the form of rye crystals. 131.89-140 g (90-95.2%) of the compound of formula I are obtained, m.p. 59-60 ° C (dichloromethane). H, 2.04; H, 38.36; N, 24.20; C, Found: C, 24.44; N, 38.56; Cl, 24.59. The IR spectrum of the compound of formula I according to the invention in chloroform has a characteristic band of the carbonyl group at 1799 cm -1.
Claims (4)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS863232A CS259381B1 (en) | 1986-05-04 | 1986-05-04 | Method of 1h-1-tetrazolylacetic acid's chloride preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS863232A CS259381B1 (en) | 1986-05-04 | 1986-05-04 | Method of 1h-1-tetrazolylacetic acid's chloride preparation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS323286A1 CS323286A1 (en) | 1988-03-15 |
| CS259381B1 true CS259381B1 (en) | 1988-10-14 |
Family
ID=5371814
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS863232A CS259381B1 (en) | 1986-05-04 | 1986-05-04 | Method of 1h-1-tetrazolylacetic acid's chloride preparation |
Country Status (1)
| Country | Link |
|---|---|
| CS (1) | CS259381B1 (en) |
-
1986
- 1986-05-04 CS CS863232A patent/CS259381B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CS323286A1 (en) | 1988-03-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2562080T3 (en) | Process and intermediate compounds to prepare integrase inhibitors | |
| CA1155444A (en) | Malonamidooxadethiacephem compounds | |
| PL80099B1 (en) | ||
| US5206386A (en) | Controlled release N-substituted pyrrolidone esters and process for the use thereof | |
| SU1149873A3 (en) | Method of obtaining threo-2-oxy-(4-methoxyphenyl)-3-(2-nitrophenylthio) propione ester and its version | |
| CS259381B1 (en) | Method of 1h-1-tetrazolylacetic acid's chloride preparation | |
| US4148817A (en) | Process and intermediates for preparing cephalosporin antibiotics | |
| US4845257A (en) | 4-halogeno-2-oxyimino-3-oxobutyric acids and derivatives | |
| US4210750A (en) | Process for the preparation of 3-carbamoyl cephalosporins using isocyanates | |
| CA1077926A (en) | Bis-trimethylsilyl cefamandole and process thereof | |
| US4150224A (en) | 7[[(1-Pyrrollyl)7 acetyl]amino]cephalosporin derivatives | |
| EP0105664B1 (en) | Process for the preparation of 3-carboxy-1-methylpyrrol-2-acetic-acid and alkali metal salts thereof | |
| CA1142173A (en) | Crystalline 3-hydroxycephalosporin solvates | |
| CN112759556B (en) | Synthetic method for preparing 5-mercapto-1, 2, 3-triazole sodium salt by one-pot method | |
| US5248822A (en) | Disulfide compound | |
| KR100432425B1 (en) | Novel method for preparation of cephem derivatives or salts thereof | |
| KR880001990B1 (en) | Process for preparing penicillin and cephalosporin intermediate compounds | |
| US4304909A (en) | Process for producing 7-(D(-)-α-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl)acetamido)-3-(5-(1-methyl-1,2,3,4-tetrazolyl)thiomethyl)-.DELTA.3 -cephem-4-carboxylic acid and a pharmaceutically acceptable salt thereof | |
| EP1254893B1 (en) | 2-halo-1-cycloalkenecarboxamides and their preparation | |
| US4331606A (en) | N-(Substituted chromone-3-carbonyl)-phenylglycine derivatives | |
| KR910004177B1 (en) | Anilinopyrimidine derivatives | |
| KR840001187B1 (en) | Method for preparing 3-thienyl malonic acid | |
| US4515958A (en) | Process for preparing 1-alkyl-5-mercaptotetrazoles | |
| US2647894A (en) | 2-chloroprocaine salt of penicillin omicron | |
| CA1081210A (en) | Bis-trimethylsilyl cefamandole and process thereof |