CH436239A - Process for the production of esters of inorganic oxo acids with acid- or temperature-sensitive alcohol components - Google Patents
Process for the production of esters of inorganic oxo acids with acid- or temperature-sensitive alcohol componentsInfo
- Publication number
- CH436239A CH436239A CH243962A CH243962A CH436239A CH 436239 A CH436239 A CH 436239A CH 243962 A CH243962 A CH 243962A CH 243962 A CH243962 A CH 243962A CH 436239 A CH436239 A CH 436239A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- temperature
- esters
- inorganic oxo
- sensitive
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims description 8
- 150000002148 esters Chemical class 0.000 title claims description 6
- 150000004715 keto acids Chemical class 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title description 3
- 239000002253 acid Substances 0.000 claims description 8
- 229960004618 prednisone Drugs 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
- 229960001810 meprednisone Drugs 0.000 claims description 5
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 5
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000012442 inert solvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 claims description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 claims description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 claims description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229960005091 chloramphenicol Drugs 0.000 claims description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 2
- 229960004544 cortisone Drugs 0.000 claims description 2
- 229960005309 estradiol Drugs 0.000 claims description 2
- 229930182833 estradiol Natural products 0.000 claims description 2
- 150000003866 tertiary ammonium salts Chemical class 0.000 claims description 2
- 229960003604 testosterone Drugs 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- PBBGSZCBWVPOOL-HDICACEKSA-N 4-[(1r,2s)-1-ethyl-2-(4-hydroxyphenyl)butyl]phenol Chemical compound C1([C@H](CC)[C@H](CC)C=2C=CC(O)=CC=2)=CC=C(O)C=C1 PBBGSZCBWVPOOL-HDICACEKSA-N 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- WRWBCPJQPDHXTJ-DTMQFJJTSA-N Methandriol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 WRWBCPJQPDHXTJ-DTMQFJJTSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229950001996 hexestrol Drugs 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960002847 prasterone Drugs 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/12—Preparation of carboxylic acid esters from asymmetrical anhydrides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/11—Esters of phosphoric acids with hydroxyalkyl compounds without further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Steroid Compounds (AREA)
Description
Verfahren zur Herstellung von Estern anorganischer Sauerstoffsäuren mit säure- oder temperaturempfindlicher Alkoholkomponente
Die Erfindung betrifft ein Verfahren zur Herstellung von Estern anorganischer Sauerstoffsäuren mit säureoder temperaturempfindlicher Alkoholkomponente, wobei man bei niedriger Temperatur, vorzugsweise 0 bis 40 C, in Gegenwart eines inerten Lösungsmittels entweder die zu veresternde anorganische Sauerstoffsäure in Gegenwart eines säurebindenden Mittels oder ein Alkali-, Erdalkali- oder tertiäres Ammoniumsalz der zu veresternden Säure mit einem niederen Halogenkohlensäurealkylester zum gemischten Säure-Kohlensäureesteranhydrid umsetzt und dann auf das erhaltene Reaktionsgemisch zur Esterbildung einen entsprechenden Alkohol einwirken lässt.
Die Verwendung von Carbonsäure-Kohlensäuremonoesteranhydriden als Acylierungsmittel ist bekannt, und das deutsche Patent 1133 727 beschreibt ein Verfahren zur Herstellung solcher Anhydride durch Umsetzung von Carbonsäuresalzen mit 0,95 bis 1,10 Äquiva- lenten Halogenkohlensäuremonoester. Die Herstellung solcher Anhydride, die in einem besonderen Arbeitsgang als Acylierungsmittel verwendet werden, ist nicht Gegenstand vorliegender Erfindung.
Beispiele temperaturempfindlicher Alkohole sind Chloramphenicol, Prednison (l-Dehydrocortison) und dessen Derivate, wie 1 6-a-Methylprednison und 1 6-p-Methylprednison, Testosteron (Androstenolon), Methylandrostendiol, Östradiol, Hexöstrol, Östron, Cortison, 1,3,5-Östratrien-3-o1-17-on.
Beispiele anorganischer Sauerstoffsäuren sind Phosphorsäure und Schwefelsäure. Man kann auch von Alkali-, Erdalkali- oder tertiären organischen Ammoniumsalzen der zu veresternden Säure ausgehen, statt ein säurebindendes Mittel zu verwenden.
Als säurebindende Mittel eignen sich insbesondere tertiäre Amine, welche die Veresterung katalytisch beeinflussen. Wenn eine Veresterung, besonders bei den für das Verfahren gewählten niedrigen Temperaturen nicht spontan einsetzt, genügen einige Tropfen mit dem Lösungsmittel verdünnten Triäthylamins, um die Umsetzung sofort in Gang zu bringen.
Beispiele inerter Lösungsmittel, d. h. solcher, die bei den Bedingungen des erfindungsgemässen Verfahrens nicht mit den Reaktionsteilnehmern reagieren, sind Dimethylformamid, Tetrahydrofuran, Acetonitril, Chloroform, Tetrachlorkohlenstoff, 1,2-Dimethoxyäthan oder Aceton. Liegen in einem der Reaktionsteilnehmer primäre oder sekundäre Aminogruppen vor, so müssen diese durch Substitution geschützt werden, um die Bildung von Amiden zu verhindern.
Die Gewinnung des Endproduktes erfolgt z. B. durch Destillation oder Fällung oder durch Extraktion mit einem nicht mischbaren Lösungsmittel.
Beispiel 1 2,5 ccm o-Phosphorsäure (850/zig) werden bei 150"C im Vakuum getrocknet, gekühlt und mit 21,5 ccm Acetonitril und 5,3 ccm Triäthylamin versetzt.
Das Reaktionsgemisch wird dann auf 200 C abgekühlt und mit 4,3 ccm Äthylchlorcarbonat, gelöst in 5 ccm Acetonitril, versetzt. Das Gemisch wird 1/4 Stunde gerührt, dann mit 3,6 g Prednison, gelöst in 16,5 ccm Acetonitril, und dann 5,3 ccm Triäthylamin zugesetzt. Das Reaktionsgemisch wird so lange gerührt, bis kein Gas mehr entsteht, dann noch 1 Stunde unter Rücklauf erhitzt und mit 28,6 ccm Methanol und38,5 ccm 2normaler methanolischen Lösung von Natriummethylat versetzt und filtriert. Das Filtrat wird bis auf 133 ccm eingeengt und mit 400 ccm Athylalkohol versetzt, wodurch das Natriumsalz des Prednison-21-phosphates ausgefällt wird. Zum Trocknen dient ein Exsikkator. Ausbeute 66 O/o der Theorie.
Beispiel 2
Das Beispiel 1 wird wiederholt, jedoch an Stelle von Prednison werden 4 g 9-a-Fluor-16ss-methylprednison umgesetzt. Ausbeute: 75 o/o 9-a-Fluor- 1 6ss-methylpred- nison-2 1 phosphatnatrium.
Beispiel 3
Das Beispiel 1 wird wiederholt, jedoch an Stelle von o-Phosphorsäure werden 3,9 g konzentrierte Schwefel säure ohne vorherige Trocknung angewendet. Es wird das Natriumsalz des Prednison-21-sulfates erhalten.
Beispiel 4
Das Beispiel 3 wird wiederholt, jedoch an Stelle von Prednison werden 4 g 9-a-Fluor- 1 6-a-methylprednis on umgesetzt. Ausbeute: 79 /o 9-a-Fluor-16-a-methylpred- nison-21-sulfatnatrium.
Beispiel 5
Das Beispiel 4 wird wiederholt, jedoch an Stelle des a-Isomeren das 16-ss-Isomere umgesetzt und 9-a-Fluor- 1 6-ss-methylprednison-2 1 -sulfatnatrium erhalten.
Process for the production of esters of inorganic oxo acids with acid- or temperature-sensitive alcohol components
The invention relates to a process for the preparation of esters of inorganic oxo acids with acidic or temperature-sensitive alcohol components, wherein either the inorganic oxyacid to be esterified in the presence of an acid-binding agent or an alkali metal, alkaline earth metal is added at low temperature, preferably 0 to 40 ° C., in the presence of an inert solvent - or the tertiary ammonium salt of the acid to be esterified is reacted with a lower alkyl halocarbonate to form the mixed acid-carbonic acid ester anhydride and then a corresponding alcohol is allowed to act on the resulting reaction mixture to form the ester.
The use of carboxylic acid-carbonic acid monoester anhydrides as acylating agents is known, and German patent 1133 727 describes a process for the preparation of such anhydrides by reacting carboxylic acid salts with 0.95 to 1.10 equivalents of halocarbonic acid monoesters. The production of such anhydrides, which are used as acylating agents in a special operation, is not the subject of the present invention.
Examples of temperature-sensitive alcohols are chloramphenicol, prednisone (l-dehydrocortisone) and its derivatives, such as 1 6-a-methylprednisone and 1 6-p-methylprednisone, testosterone (androstenolone), methylandrostendiol, estradiol, hexoestrol, estrone, cortisone, 1,3, 5-oestatria-3-o1-17-one.
Examples of inorganic oxo acids are phosphoric acid and sulfuric acid. You can also start from alkali, alkaline earth or tertiary organic ammonium salts of the acid to be esterified, instead of using an acid-binding agent.
Tertiary amines, which catalytically influence the esterification, are particularly suitable as acid-binding agents. If an esterification does not start spontaneously, especially at the low temperatures chosen for the process, a few drops of triethylamine diluted with the solvent are sufficient to start the reaction immediately.
Examples of inert solvents, i. H. those which do not react with the reactants under the conditions of the process according to the invention are dimethylformamide, tetrahydrofuran, acetonitrile, chloroform, carbon tetrachloride, 1,2-dimethoxyethane or acetone. If there are primary or secondary amino groups in one of the reactants, they must be protected by substitution in order to prevent the formation of amides.
The final product is obtained, for. B. by distillation or precipitation or by extraction with an immiscible solvent.
Example 1 2.5 cc of o-phosphoric acid (850 / zig) are dried at 150 "C in a vacuum, cooled and mixed with 21.5 cc of acetonitrile and 5.3 cc of triethylamine.
The reaction mixture is then cooled to 200 ° C. and 4.3 cc of ethyl chlorocarbonate dissolved in 5 cc of acetonitrile is added. The mixture is stirred for 1/4 hour, then 3.6 g of prednisone, dissolved in 16.5 cc of acetonitrile, and then 5.3 cc of triethylamine are added. The reaction mixture is stirred until no more gas is formed, then heated under reflux for a further 1 hour, mixed with 28.6 cc of methanol and 38.5 cc of 2 normal methanolic solution of sodium methylate and filtered. The filtrate is concentrated to 133 cc and mixed with 400 cc of ethyl alcohol, whereby the sodium salt of prednisone-21-phosphate is precipitated. A desiccator is used for drying. Yield 66% of theory.
Example 2
Example 1 is repeated, but instead of prednisone, 4 g of 9-α-fluoro-16ss-methylprednisone are reacted. Yield: 75 o / o 9-α-fluoro-1 6ss-methylprednison-2 1 phosphate sodium.
Example 3
Example 1 is repeated, but instead of o-phosphoric acid, 3.9 g of concentrated sulfuric acid are used without prior drying. The sodium salt of prednisone-21-sulfate is obtained.
Example 4
Example 3 is repeated, but instead of prednisone, 4 g of 9-α-fluoro-1 6-a-methylprednisone are reacted. Yield: 79 / o 9-α-fluoro-16-α-methylprednisone-21-sulfate sodium.
Example 5
Example 4 is repeated, but instead of the α-isomer the 16-β-isomer is converted and 9-α-fluoro-1 6-β-methylprednisone-2 1 -sulfate sodium is obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PT3814361 | 1961-03-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH436239A true CH436239A (en) | 1967-05-31 |
Family
ID=20081602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH243962A CH436239A (en) | 1961-03-03 | 1962-02-28 | Process for the production of esters of inorganic oxo acids with acid- or temperature-sensitive alcohol components |
Country Status (5)
| Country | Link |
|---|---|
| BE (1) | BE614636A (en) |
| CH (1) | CH436239A (en) |
| DE (1) | DE1200822B (en) |
| GB (1) | GB970789A (en) |
| NL (1) | NL275507A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5874468A (en) * | 1996-12-26 | 1999-02-23 | Yissum | Brain targeted low molecular weight hydrophobic antioxidant compounds |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1093797B (en) * | 1959-01-31 | 1960-12-01 | Bayer Ag | Process for the production of carboxylic acid esters |
| DE1111187B (en) * | 1959-11-27 | 1961-07-20 | Shell Int Research | Process for the preparation of phosphoric acid esters, phosphoric amides or carbonic anhydrides |
-
0
- NL NL275507D patent/NL275507A/xx unknown
-
1962
- 1962-02-28 CH CH243962A patent/CH436239A/en unknown
- 1962-03-01 DE DEV22113A patent/DE1200822B/en active Pending
- 1962-03-02 BE BE614636A patent/BE614636A/en unknown
- 1962-03-05 GB GB842762A patent/GB970789A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB970789A (en) | 1964-09-23 |
| BE614636A (en) | 1962-07-02 |
| NL275507A (en) | |
| DE1200822B (en) | 1965-09-16 |
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