DE3009063C2 - Process for the preparation of α-6-deoxy-5-hydroxytetracycline - Google Patents
Process for the preparation of α-6-deoxy-5-hydroxytetracyclineInfo
- Publication number
- DE3009063C2 DE3009063C2 DE3009063A DE3009063A DE3009063C2 DE 3009063 C2 DE3009063 C2 DE 3009063C2 DE 3009063 A DE3009063 A DE 3009063A DE 3009063 A DE3009063 A DE 3009063A DE 3009063 C2 DE3009063 C2 DE 3009063C2
- Authority
- DE
- Germany
- Prior art keywords
- deoxy
- hydroxytetracycline
- rhodium
- reaction
- 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.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims description 14
- 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 title 1
- 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 10
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 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
- 235000010323 ascorbic acid Nutrition 0.000 claims description 4
- 239000011668 ascorbic acid Substances 0.000 claims description 4
- 229960005070 ascorbic acid Drugs 0.000 claims description 4
- 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 claims description 3
- 239000002211 L-ascorbic acid Substances 0.000 claims description 3
- 235000000069 L-ascorbic acid Nutrition 0.000 claims description 3
- 238000005984 hydrogenation reaction Methods 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 8
- 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
- -1 chloromethylene tetracycline Chemical class 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000010948 rhodium 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
- 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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 238000007210 heterogeneous catalysis Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 230000000707 stereoselective effect Effects 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 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
- 241000252073 Anguilliformes Species 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
- 238000000862 absorption spectrum Methods 0.000 description 1
- 238000004458 analytical method Methods 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
- 229910052799 carbon Inorganic materials 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
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 239000002815 homogeneous catalyst Substances 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
- 238000012009 microbiological test Methods 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
- 239000000376 reactant Substances 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
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000000725 suspension Substances 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Description
2020th
Die Erfindung betrifft ein Verfahren zur Hersteltung von «-e-Desoxy-S-hydroxytetracyclin mittels Hydrogenolyse von lla-Brom-ö-desmethyl-e-desoxy-e-methylen-5-hydroxytetracyclin mit Rhodium auf Kohle als Katalysator in Gegenwart von L(+)-Ascorbinsäure gemäß den vorstehenden Ansprüchen.The invention relates to a method of manufacture of «-e-deoxy-S-hydroxytetracycline by means of hydrogenolysis of lla-bromo-ö-desmethyl-e-deoxy-e-methylene-5-hydroxytetracycline with rhodium on carbon as a catalyst in the presence of L (+) - ascorbic acid according to the preceding claims.
«-6- Desoxy-5-hydroxytetracyclin mit dem Trivialnamen Doxycyciin ist ein bekanntes antibiotisches Arzneimittel zur Behandlung von verschiedenen Infektionskrankheiten (Antibiotikum mit breitem Spektrum).«-6- Deoxy-5-hydroxytetracycline with the common name Doxycyciin is a well-known antibiotic medicine used to treat various infectious diseases (Broad spectrum antibiotic).
Es ist bekannt, daß 6-Methylentetracyclin, 1 Ia-HaIo-6-methylentetracyclin, insbesondere Ua-Chlor-methylentetracyclin, und deren Säuresalze oder Komplexe mit mehrwertigen Metallen durch heterogene Katalyse in Gegenwart von Edelmetallen mit Wasserstoff reduziert werden können und dabei »- und jS-6-Desoxytetracycline in etwa gleichen Mengen erhalten werden (US-PS 32 00 149). Da nur das «-Isomere medizinisch interessant ist, wurden später zahlreiche neue Methoden undIt is known that 6-methylenetetracycline, 1 Ia-Halo-6-methylenetetracycline, especially including chloromethylene tetracycline, and their acid salts or complexes with polyvalent metals by heterogeneous catalysis in Presence of noble metals can be reduced with hydrogen and thereby »- and jS-6-Deoxytetracycline can be obtained in approximately equal amounts (US-PS 32 00 149). Since only the «isomer is medically interesting is, numerous new methods and were later introduced
CH2OHCH 2 OH
N(CHj)2 N (CHj) 2
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 34 44 198) oder deren Aufbringen auf spezielle Träger (PT-PS 52 217) eine geringfügig größere Menge des aals /Msomeren zu gewinnen. Als Katalysatoren sind beschrieben noch Palladium auf Kohle mit Hydrazin als Wasserstoffquelle (DE-PS 2131944), Palladium auf Kohle mit einer großen Oberfläche, mit Teilchengrößen unter 10 Ä (HU-PS 12 042), ferner die Reduktion mit Platinoxid (DE-OS 21 36 621, GB-PS 12 96 340). Gute Ergebnisse soll Rhodium auf Kohle in Gegenwart von N-Methylpyrrolidon, Triphenylphosphin und Beschleunigern — Säuren oder SnCI2 — aufweisen (DE-PS 24 18499).Modifications of the known methods developed, the main purpose of which was to obtain the largest possible amounts of the α-isomer. It was possible to gain a slightly larger amount of the eels / msomers by poisoning noble metals as catalysts (US Pat. No. 3,444,198) or applying them to special supports (PT-PS 52 217). The catalysts described are palladium on charcoal with hydrazine as the hydrogen source (DE-PS 2131944), palladium on charcoal with a large surface area, with particle sizes below 10 Å (HU-PS 12 042), and also reduction with platinum oxide (DE-OS 21 36 621, GB-PS 12 96 340). Rhodium on carbon in the presence of N-methylpyrrolidone, triphenylphosphine and accelerators - acids or SnCl 2 - is said to have good results (DE-PS 24 18499).
Neben heterogener Katalyse sind Hydrierungen mit homogenen Katalysatoren bekannt, das sind insbesondere Rhodiumhalogenkomplexe, die tertiäre Phosphine, Arsine oder Stilebene als Liganden enthalten (US-PS 36 39 439, DE-PS 23 08 227 und 24 46 587), ferner Chlorbisäthylenrhodiumdimere mit Triphenylphosphin (DE-PS 24 03 714) und schließlich Rhodiumacetat mit Phenylphosphin (DE-PS 25 54 564).In addition to heterogeneous catalysis, hydrogenations with homogeneous catalysts are known, in particular Rhodium halogen complexes containing tertiary phosphines, arsines or stilplane ligands (US-PS 36 39 439, DE-PS 23 08 227 and 24 46 587), also chlorobisethylene rhodium dimers with triphenylphosphine (DE-PS 24 03 714) and finally rhodium acetate with phenylphosphine (DE-PS 25 54 564).
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 <x-6-Desoxy-5-hydroxy tetracyclin reduziert wird (US-PS 39 07 890).One interesting method is using 6-methylene-5-hydroxytetracycline in the presence of dicobalt octacarbonyl, triphenylphosphine and hydrochloric acid without hydrogen and reducing tetracycline to <x-6-deoxy-5-hydroxy in an inert atmosphere of nitrogen or argon (US-PS 39 07 890).
Nun wurde gefunden, daß lla-Brom-6-desmethyl-6-desoxy-ö-methylen-S-hydroxytetracyclin bzw. dessen Salze oder Komplexe (wie ein Sulfosalicylat) in einer Reaktionsstufe mit Wasserstoff in Gegenwart von Rhodium als Katalysator und L( +^Ascorbinsäure als Vermittler in einer stereospezifischen Reduktion dehaloginiert und hydriert werden, und zwar gemäß dem folgenden Reaktionsschema:It has now been found that Ila-bromo-6-desmethyl-6-deoxy-ö-methylene-S-hydroxytetracycline or its salts or complexes (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 dehaloginated in a stereospecific reduction and hydrogenated according to the following reaction scheme:
H3CH 3 C
OH N(CHj)2 OH N (CHj) 2
Rh/C,H2 Rh / C, H 2
CONH2 CONH 2
OHOH
CONH2 CONH 2
OH OOH O
OH O OH OOH O OH O
Gemäß vorliegender Erfindung wird die Reaktion mit Wasserstoff in Gegenwart von 0,1 bis 0,3 Mol von 5prozentigem Rhodium auf Kohle und 1-Moläquivalent L( + )-Ascorbinsäure in Alkohol unter Druck von 3,04 bis 30,4 bar bei Raum- oder erhöhter Temperatur durchgeführt. Das Reaktionsprodukt ist praktisch ausschließlich «-e-Desoxy-S-hydroxytetracyclin. Die Reduktion ist in einem solchen Maße stereospezifisch, daß irgendwelche Änderungen der Reaktanten, das Katalysators oder des Vermittlers zur Gewinnung von größeren Mengen von /Msomeren, anderen Verbindungen, wie Anhydroderivaten, ö-Desmethyl-e-desoxy-ömethylen-5-hydroxy-tetracyclin u. a. führen.According to the present invention, the reaction with hydrogen in the presence of 0.1 to 0.3 moles of 5 percent rhodium on carbon and 1 molar equivalent of L (+) -ascorbic acid in alcohol under a pressure of 3.04 carried out up to 30.4 bar at room or elevated temperature. The reaction product is practical exclusively «-e-deoxy-S-hydroxytetracycline. the Reduction is stereospecific to such an extent that any changes in the reactants, the Catalyst or intermediary for the production of larger amounts of / Msomers, other compounds, such as anhydroderivaten, ö-desmethyl-e-deoxy-ömethylene-5-hydroxy-tetracycline i.a. to lead.
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.An advantage of the present invention, in addition to the excellent stereospecificity of the reaction, is its simple implementation 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 5prozentigem Rhodium auf Kohle und 176 mg (1 mMol) L( +^Ascorbinsäure in 75 ml Methanol wird eine Lösung von 740 mg (1 mMol) 1 la-Brom-6-desmethyl-6-desoxy-e-methylen-S-hydroxytetracyclinsuIfonsalicylat in 75 ml Methanol gegeben. Das Reaktionsgemisch wird dann unter denselben Bedingungen entlüftet und unter Druck von 5,07 bar 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 1 la-bromo-6-desmethyl-6-deoxy-e-methylene-S-hydroxytetracycline sulfonic salicylate given in 75 ml of methanol. The reaction mixture is then vented under the same conditions and under Pressure of 5.07 bar 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 mittels Chlorofrom verteilt, die wäßrige Schicht wird auf ein kleines Volumen (etwa 5 ml) eingeengt und über Nacht bei 0cC stehengelassen.After filtering off the catalyst, the filtrate is concentrated to dryness. The residue is dissolved in water and distributed by means of chlorofrom, the aqueous layer is concentrated to a small volume (about 5 ml) and left to stand at 0 ° C. overnight.
Das kristalline Produkt wird abgesaugt und mit Äthanol gewaschen. Rs werden 300 mg des Produktes (63% der Theorie, bezogen auf die freie Base) erhalten. Das Ergebnis der Dünnschichtchromatographie zeigt praktisch ausschließlich die Anwesenheit von «-e-Desoxy-5-hydroxytetracyclin. The crystalline product is filtered off and washed with ethanol washed. Rs 300 mg of the product (63% of theory, based on the free base) are obtained. That The result of thin-layer chromatography shows almost exclusively the presence of -e-deoxy-5-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.
C22H24N2O8- HCl (480.90)
Ber.in%:C 22 H 24 N 2 O 8 - HCl (480.90)
Ber. In%:
C 54,90; H 5,20; N 5,83; Cl 7,83.
Gef.in°/o:
C 54,72; H 5,46; N 5,56; Cl 7,44.C 54.90; H 5.20; N 5.83; Cl 7.83.
Found in ° / o:
C 54.72; H 5.46; N 5.56; Cl 7.44.
[α]?= -272° (C=O^OJ η H2SO4)
UV-Absorptionsspektrum (0,1 η H2SO4):[α]? = -272 ° (C = O ^ OJ η H 2 SO 4 )
UV absorption spectrum (0.1 η H 2 SO 4 ):
Am„,218,.767und243nmA m ", 218, .767 and 243 nm
(log ε 4,11,4,26 und 4,15)
Mikrobiologischer Test:(log ε 4, 11, 4, 26 and 4.15)
Microbiological test:
1 mg = 871,0 Einheiten.1 mg = 871.0 units.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied ausgeführt, daß statt Methanoi Äthanol verwendet wird. Ausbeute: wie in Beispiel 1.The procedure is carried out as in Example 1 with the difference that instead of methanol, ethanol is used. 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 instead of methanol is used.
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 5prozentigern
Rhodium auf Kohle 0,450 g verwendet werden.
Ausbeute: 270 mg.. The process 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 10,13 bar abläuft.
Ausbeute: 293 mg.The process is carried out as in Example 4 with the difference that the reaction takes place under a pressure of 10.13 bar.
Yield: 293 mg.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter
einem Druck von 20,26 bar abläuft. Die Reaktionszeit wird auf 1 Stunde vermindert.
Ausbeute: wie in Beispiel 1.The process is carried out as in Example 1 with the difference that the reaction takes place under a pressure of 20.26 bar. The reaction time is reduced to 1 hour.
Yield: as in example 1.
Das Verfahren wird wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter Druck von 152 bar erfolgt.The procedure is carried out as in Example 1 with the difference that the reaction under Pressure of 152 bar takes place.
Ausbeute: 316 mg (67% der Theorie, bezogen auf die freie Base).Yield: 316 mg (67% of theory, based on the free base).
Das Verfahren w rd wie in Beispiel 1 mit dem Unterschied durchgeführt, daß die Reaktion unter einem Druck von 3,04 bar und bei einer Temperatur von 4O0C verläuft.The method ng carried out as in Example 1 with the difference that the reaction under a pressure of 3.04 bar and at a temperature of 4O 0 C extends.
Ausbeute: wie in Beispiel 1.Yield: as in example 1.
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 DE3009063A1 (en) | 1980-09-18 |
| DE3009063C2 true 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) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1430859A (en) * | 1960-05-23 | 1966-05-25 |
-
1979
- 1979-03-12 YU YU598/79A patent/YU41480B/en unknown
-
1980
- 1980-02-20 GB GB8005761A patent/GB2046248B/en not_active Expired
- 1980-02-20 CH CH137880A patent/CH644583A5/en not_active IP Right Cessation
- 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
Also Published As
| Publication number | Publication date |
|---|---|
| CH644583A5 (en) | 1984-08-15 |
| ATA115180A (en) | 1983-08-15 |
| YU59879A (en) | 1982-10-31 |
| GB2046248A (en) | 1980-11-12 |
| GB2046248B (en) | 1982-12-01 |
| YU41480B (en) | 1987-08-31 |
| AT374169B (en) | 1984-03-26 |
| IT1129806B (en) | 1986-06-11 |
| IT8067379A0 (en) | 1980-03-11 |
| DE3009063A1 (en) | 1980-09-18 |
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