DE3009063A1 - METHOD FOR PRODUCING ALPHA -6-DESOXY-5-HYDROXY-TETRACYCLIN - Google Patents
METHOD FOR PRODUCING ALPHA -6-DESOXY-5-HYDROXY-TETRACYCLINInfo
- Publication number
- DE3009063A1 DE3009063A1 DE19803009063 DE3009063A DE3009063A1 DE 3009063 A1 DE3009063 A1 DE 3009063A1 DE 19803009063 DE19803009063 DE 19803009063 DE 3009063 A DE3009063 A DE 3009063A DE 3009063 A1 DE3009063 A1 DE 3009063A1
- Authority
- DE
- Germany
- Prior art keywords
- hydroxytetracycline
- deoxy
- reaction
- rhodium
- carried out
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 3
- 238000000034 method Methods 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 10
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000010948 rhodium Substances 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 230000000707 stereoselective effect Effects 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000005476 soldering Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- CIWBSHSKHKDKBQ-SZSCBOSDSA-N 2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one Chemical compound OC[C@H](O)C1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-SZSCBOSDSA-N 0.000 description 4
- 239000002211 L-ascorbic acid Substances 0.000 description 4
- 235000000069 L-ascorbic acid Nutrition 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000007210 heterogeneous catalysis Methods 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 2
- 229940071103 sulfosalicylate Drugs 0.000 description 2
- XIYOPDCBBDCGOE-IWVLMIASSA-N (4s,4ar,5s,5ar,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methylidene-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C=C1C2=CC=CC(O)=C2C(O)=C2[C@@H]1[C@H](O)[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O XIYOPDCBBDCGOE-IWVLMIASSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- -1 anhydro derivatives Chemical class 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- RBFQJDQYXXHULB-UHFFFAOYSA-N arsane Chemical group [AsH3] RBFQJDQYXXHULB-UHFFFAOYSA-N 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- MQIKJSYMMJWAMP-UHFFFAOYSA-N dicobalt octacarbonyl Chemical group [Co+2].[Co+2].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-].[O+]#[C-] MQIKJSYMMJWAMP-UHFFFAOYSA-N 0.000 description 1
- 229960003722 doxycycline Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 150000003003 phosphines Chemical group 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 150000003283 rhodium Chemical class 0.000 description 1
- ITDJKCJYYAQMRO-UHFFFAOYSA-L rhodium(2+);diacetate Chemical compound [Rh+2].CC([O-])=O.CC([O-])=O ITDJKCJYYAQMRO-UHFFFAOYSA-L 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 150000001629 stilbenes Chemical group 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/65—Tetracyclines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
Description
BESCHREIBUNGDESCRIPTION
Die Erfindung betrifft ein Verfahren zur Herstellung von &-6-Desoxy-5-hydroxytetracyclin mittels Hydrogenolyse von 11 a-Brom-e-demethyl-e-desoxy-e-methylen-S-hydroxytetracyclin mit Rhodium auf Kohle als Katalysator in Gegenwart von L(+)-Ascorbinsäure. The invention relates to a process for the production of & -6-deoxy-5-hydroxytetracycline by means of hydrogenolysis of 11 a-bromo-e-demethyl-e-deoxy-e-methylene-S-hydroxytetracycline with rhodium on carbon as a catalyst in the presence of L (+) - ascorbic acid.
ß_6_Desoxy-5-hydroxytetracyclLn mit dem Common Name Doxycyclin ist ein bekanntes antibiotisches Arzneimittel zur Behandlung von verschiedenen Infektionskrankheiten (Antibiotikum mit breitem Spektrum.ß_6_Desoxy-5-hydroxytetracycline with the common name Doxycycline is a well-known antibiotic medicine used to treat various infectious diseases (antibiotic with wide range.
Es ist bekannt, daß 6-Methylentetracyclin, 11a-Halo-6-methylentetracyclin, insbesondere Ha-Chlor-methylentetracyclin, und deren Säuresalze oder Komplexe mit mehrwertigen Metallen durch heterogene Katalyse in Gegenwart von Edelmetallen mit Wasserstoff reduziert werden können und dabei Or- und ß-6-Desoxytetracycline in etwa gleichen Mengen erhalten werden (US-PS 3 200 149). Da nur das α-Isomere medizinisch interessant ist, wurden später zahlreiche neue Methoden und Abänderungen der bekannten Methoden entwickelt, die es zum Hauptzweck hatten, möglichst große Mengen des α-Isomeren zu gewinnen. So gelang es, durch Vergiftung von Edelmetallen als Katalysatoren (US-PS 3 444 198) oder deren Aufbringen auf spezielle Träger (PT-PS 52 217) eine geringfügig größere Menge des cc- als ß-Isomeren zu gewinnen. Als Katalysatoren sind beschrieben noch Palladium auf Kohle mit Hydrazin als Wasserstoffquelle (DE-PS 2 131 944), Palladium auf Kohle mit einer großen Oberfläche, mit Teilchengrößen unter 10 1 (HU-PS 12 042), ferner die Reduktion mit Platinoxid (DE-OS 2 136 621, GB-PS 1 296 340). Gute Ergebnisse soll Rhodium auf Kohle in Gegenwart von N-Methylpyrrolidon, Triphenylphosphin und Beschleunigern - Säuren oder SnCl2 - aufweisen (DE-PS 2 418 499).It is known that 6-methylentetracycline, 11a-halo-6-methylentetracycline, in particular Ha-chloromethylene tetracycline, and their acid salts or complexes with polyvalent metals can be reduced by heterogeneous catalysis in the presence of noble metals with hydrogen and thereby Or- and ß -6-Deoxytetracyclines can be obtained in approximately equal amounts (US Pat. No. 3,200,149). Since only the α-isomer is of medical interest, numerous new methods and modifications of the known methods were later developed, the main purpose of which was to obtain the largest possible quantities of the α-isomer. By poisoning noble metals as catalysts (US Pat. No. 3,444,198) or applying them to special supports (PT Pat. No. 52,217), it was possible to obtain a slightly larger amount of the cc than the beta isomer. The catalysts described are palladium on carbon with hydrazine as the hydrogen source (DE-PS 2 131 944), palladium on carbon with a large surface area, with particle sizes below 10 1 (HU-PS 12 042), and also reduction with platinum oxide (DE- OS 2 136 621, GB-PS 1 296 340). Rhodium on carbon in the presence of N-methylpyrrolidone, triphenylphosphine and accelerators - acids or SnCl 2 - is said to have good results (DE-PS 2 418 499).
030038/0853030038/0853
Neben heterogener Katalyse sind Hydrierungen mit homogenen Katalysatoren bekannt, das sind insbesondere Rhodiumhalokomplexe, die tertiäre Phosphine, Arsine oder Stilbene als Liganden enthalten (US-PS 3 639 439, DE-PS 2 308 227 und 2 446 587), ferner Chlorbisäthylenrhodiumdimer mit Triphenylphosphin (DE-PS 2 403 714) und schließlich Rhodiumdiacetat mit Phenylphosphin (DE-PS 2 554 564).In addition to heterogeneous catalysis, hydrogenations with homogeneous catalysts are known, in particular rhodium halo complexes, which contain tertiary phosphines, arsines or stilbenes as ligands (US Pat. No. 3,639,439, German Pat. No. 2,308,227 and 2,446,587), as well as chlorobisethylene rhodium dimer with triphenylphosphine (DE-PS 2 403 714) and finally rhodium diacetate with phenylphosphine (DE-PS 2 554 564).
Interessant ist eine Methode, wobei 6-Methylen-5-hydroxytetracyclin in Gegenwart von Dicobaltoctacarbonyl, Triphenylphosphin und Salzsäure ohne Wasserstoff und in einer Inertatmosphäre von Stickstoff oder Argon zu a-6-Desoxy-5-hydroxytetracyclin reduziert wird (US-PS 3 907 890).One interesting method is using 6-methylene-5-hydroxytetracycline in the presence of dicobalt octacarbonyl, triphenylphosphine and hydrochloric acid without hydrogen and in an inert atmosphere is reduced by nitrogen or argon to α-6-deoxy-5-hydroxytetracycline (U.S. Patent 3,907,890).
Nun wurde gefunden, daß iia-Brom-e-demethyl-ö-desoxy-ömethylen-5-hydroxytetracyclin bzw. dessen Salz oder Komplex (wie ein Sulfosalicylat) in einer Reaktionsstufe mit Wasserstoff in Gegenwart von Rhodium als Katalysator und L(+)-Ascorbinsäure als Vermittler einer stereospezifischen Reduktion dehalogeniert und hydriert wird, und zwar gemäß dem folgenden Reaktionsschema:It has now been found that iia-bromo-e-demethyl-ö-deoxy-ömethylene-5-hydroxytetracycline or its salt or complex (such as a sulfosalicylate) in a reaction stage with hydrogen in the presence of rhodium as a catalyst and L (+) - ascorbic acid as a mediator of a stereospecific reduction is dehalogenated and hydrogenated according to the following reaction scheme:
Rh/CRh / C
CONH.CONH.
Ascorbinsäure Ascorbic acid
OH 0OH 0
Gemäß vorliegender Erfindung wird die Reaktion mit Wasserstoff in Gegenwart von 0,1-0,3 Mol von 5-prozentigem Rhodium auf Kohle und 1 Moläquivalent L(+)-Ascorbinsäure in Alkohol unter Druck von 3-30 Atm bei Raum- oder erhöhter Temperatur durchgeführt. Das Reaktionsprodukt ist praktisch ausschließlich a-6- Desoxy -5-hydroxytetracyclin. Die Reduktion ist in einem solchen Maße stereospezifisch, daß irgendwelche Xnde-In accordance with the present invention, the reaction with hydrogen is carried out in the presence of 0.1-0.3 moles of 5 percent rhodium on charcoal and 1 molar equivalent of L (+) - ascorbic acid in alcohol under pressure of 3-30 atm at room or elevated temperature carried out. The reaction product is practically exclusive α-6 deoxy -5-hydroxytetracycline. The reduction is in stereospecific to such an extent that any Xnde-
030038/0853030038/0853
rungen der Reaktanten, des Katalysators oder des Vermittlers zur Gewinnung von größeren Mengen von ß-Isomeren, anderen Verbindungen, wie Anhydroderivaten, 6-Demethyl-6-desoxy-6-methylen-5-hydroxy-tetracyclin u.a. führen.ments of the reactants, the catalyst or the mediator to obtain larger amounts of ß-isomers, others Compounds such as anhydro derivatives, 6-demethyl-6-deoxy-6-methylene-5-hydroxy-tetracycline lead among others.
Ein Vorteil der vorliegenden Erfindung ist neben hervorragender Stereospezifität der Reaktion ihre einfache Durchführung unter Verwendung eines einfachen, gut zugänglichen und in jedem Sinne harmlosen Vermittlers.One advantage of the present invention, in addition to the excellent stereospecificity of the reaction, is that it is easy to carry out using a simple, accessible and in every sense harmless intermediary.
Die Erfindung wird durch die folgenden Beispiele erläutert:The invention is illustrated by the following examples:
Zu einer entlüfteten Suspension von 1,12 g von 5-prozentigem Rhodium auf Kohle und 176 mg (1 mMol) L(+)-Ascorbinsäure in 75 ml Methanol wird eine Lösung von 740 mg (1 mMol) 1Ia-Bromö-demethyl-o-desoxy-ö-methylen-S-hydroxytetracyclinsulfosalicylat in 75 ml Methanol gegeben. Das Reaktionsgemisch wird dann unter denselben Bedingungen entlüftet und unter Druck von 5 atm und bei Raumtemperatur während 3 Stunden hydriert.To a deaerated suspension of 1.12 g of 5 percent rhodium on carbon and 176 mg (1 mmol) L (+) - ascorbic acid in 75 ml of methanol is a solution of 740 mg (1 mmol) of 1Ia-bromo-demethyl-o-deoxy-o-methylene-S-hydroxytetracycline sulfosalicylate given in 75 ml of methanol. The reaction mixture is then deaerated under the same conditions and under pressure of 5 atm and hydrogenated at room temperature for 3 hours.
Nach Abfiltrierung des Katalysators wird das Filtrat bis zur Trockne eingeengt. Der Rückstand wird in Wasser gelöst und mittles Chloroform verteilt. Die wässrige Schicht wird auf ein kleines Volumen (etwa 5 ml) eingeengt und über Nacht bei O0C stehengelassen. Das kristallinische Produkt wird abgesaugt und mit Äthanol gewaschen. Es werden 300 ml des Produktes (63 %, berechnet auf die Basis])erhalten. Das Ergebnis der Dünnschichtchromatographie zeigt eine praktisch ausschließliche Anwesenheit von a-o-Desoxy-S-hydroxytetracyclin.After filtering off the catalyst, the filtrate is concentrated to dryness. The residue is dissolved in water and partitioned with chloroform. The aqueous layer is concentrated to a small volume (about 5 ml) and left to stand at 0 ° C. overnight. The crystalline product is filtered off with suction and washed with ethanol. 300 ml of the product (63 %, calculated on the basis]) are obtained. The result of thin-layer chromatography shows a practically exclusive presence of ao-deoxy-S-hydroxytetracycline.
Das Produkt wird zwecks Analyse nach üblichen Methoden gereinigt. Alle analytischen Angaben sind identisch mit den Angaben für eine authentische Probe.The product is purified by standard methods for analysis. All analytical information is identical to the information for an authentic sample.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied ausgeführt, daß statt Methanol Äthanol verwendet wird.The procedure is carried out as in Example 1 with the difference that ethanol is used instead of methanol.
030038/0853030038/0853
- 6 Ausbeute: wie in Beispiel 1.- 6 yield: as in example 1.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied ausgeführt, daß statt Methanol Isopropanol verwendet wird.The procedure is carried out as in Example 1 with the difference that isopropanol is used instead of methanol.
Ausbeute: wie in Beispiel 1.Yield: as in example 1.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied ausgeführt,
daß statt 1,12 g von 5-prozentigem Rhodium auf Kohle 0,450 g verwendet werden.
Ausbeute: 270 mg.The procedure is carried out as in Example 1 with the difference that 0.450 g are used instead of 1.12 g of 5 percent rhodium on carbon.
Yield: 270 mg.
Das Verfahren wird wie in Beispiel 4 mit dem Unterschied durchgeführt, daß die Reaktion unter einem Druck von 10 atm
abläuft.
Ausbeute: 293 mg.The procedure is carried out as in Example 4 with the difference that the reaction takes place under a pressure of 10 atm.
Yield: 293 mg.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter einem Druck von 20 atm abläuft. Die Reaktionszeit wird auf 1 Stunde vermindert.The procedure is carried out as in Example 1 with the difference that the reaction is carried out under a pressure of 20 atm expires. The reaction time is reduced to 1 hour.
Ausbeute: wie in Beispiel 1.Yield: as in example 1.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter Druck von 15 atm erfolgt. Ausbeute: 316 mg (67 %, berechnet auf die Basis).The procedure is carried out as in Example 1 with the difference that the reaction is carried out under a pressure of 15 atm. Yield: 316 mg (67 % calculated on the basis).
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter einem Druck von 3 atm und bei einer Temperatur von 40°C verläuft. Ausbeute: wie in Beispiel 1.The procedure is carried out as in Example 1 with the difference that the reaction is carried out under a pressure of 3 atm and runs at a temperature of 40 ° C. Yield: as in example 1.
030038/0853030038/0853
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU598/79A YU41480B (en) | 1979-03-12 | 1979-03-12 | Process for obtaining alpha-6-deoxy-5-hydroxytetracycline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3009063A1 true DE3009063A1 (en) | 1980-09-18 |
| DE3009063C2 DE3009063C2 (en) | 1982-10-28 |
Family
ID=25550617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3009063A Expired DE3009063C2 (en) | 1979-03-12 | 1980-03-10 | Process for the preparation of α-6-deoxy-5-hydroxytetracycline |
Country Status (6)
| Country | Link |
|---|---|
| AT (1) | AT374169B (en) |
| CH (1) | CH644583A5 (en) |
| DE (1) | DE3009063C2 (en) |
| GB (1) | GB2046248B (en) |
| IT (1) | IT1129806B (en) |
| YU (1) | YU41480B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3200149A (en) * | 1960-05-23 | 1965-08-10 | Pfizer & Co C | alpha-6-deoxytetracycline derivatives and process |
-
1979
- 1979-03-12 YU YU598/79A patent/YU41480B/en unknown
-
1980
- 1980-02-20 CH CH137880A patent/CH644583A5/en not_active IP Right Cessation
- 1980-02-20 GB GB8005761A patent/GB2046248B/en not_active Expired
- 1980-03-03 AT AT0115180A patent/AT374169B/en not_active IP Right Cessation
- 1980-03-10 DE DE3009063A patent/DE3009063C2/en not_active Expired
- 1980-03-11 IT IT67379/80A patent/IT1129806B/en active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3200149A (en) * | 1960-05-23 | 1965-08-10 | Pfizer & Co C | alpha-6-deoxytetracycline derivatives and process |
Also Published As
| Publication number | Publication date |
|---|---|
| ATA115180A (en) | 1983-08-15 |
| IT8067379A0 (en) | 1980-03-11 |
| YU59879A (en) | 1982-10-31 |
| AT374169B (en) | 1984-03-26 |
| GB2046248A (en) | 1980-11-12 |
| YU41480B (en) | 1987-08-31 |
| CH644583A5 (en) | 1984-08-15 |
| DE3009063C2 (en) | 1982-10-28 |
| IT1129806B (en) | 1986-06-11 |
| GB2046248B (en) | 1982-12-01 |
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