DE902257C - Process for the preparation of acyl derivatives of the enol form of codeinone - Google Patents
Process for the preparation of acyl derivatives of the enol form of codeinoneInfo
- Publication number
- DE902257C DE902257C DEK10625A DEK0010625A DE902257C DE 902257 C DE902257 C DE 902257C DE K10625 A DEK10625 A DE K10625A DE K0010625 A DEK0010625 A DE K0010625A DE 902257 C DE902257 C DE 902257C
- Authority
- DE
- Germany
- Prior art keywords
- codeinone
- preparation
- acyl derivatives
- enol form
- room temperature
- 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
- XYYVYLMBEZUESM-CMKMFDCUSA-N codeinone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=CC(=O)[C@@H]1OC1=C2C3=CC=C1OC XYYVYLMBEZUESM-CMKMFDCUSA-N 0.000 title claims description 13
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 5
- 125000002252 acyl group Chemical group 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 125000002587 enol group Chemical group 0.000 title claims 2
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000003776 cleavage reaction Methods 0.000 claims description 4
- RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 claims description 3
- 230000007017 scission Effects 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 150000004665 fatty acids Chemical class 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 229940075930 picrate Drugs 0.000 description 6
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 4
- FQXXSQDCDRQNQE-UHFFFAOYSA-N markiertes Thebain Natural products COC1=CC=C2C(N(CC3)C)CC4=CC=C(OC)C5=C4C23C1O5 FQXXSQDCDRQNQE-UHFFFAOYSA-N 0.000 description 4
- FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 4
- 229930003945 thebaine Natural products 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 229960004126 codeine Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- -1 enol methyl ether Chemical class 0.000 description 2
- 150000002085 enols Chemical group 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- MYOPYNHXINLPTK-UHFFFAOYSA-N (5-acetyloxy-6-methoxyphenanthren-3-yl) acetate Chemical compound C1=C(OC(C)=O)C=C2C3=C(OC(C)=O)C(OC)=CC=C3C=CC2=C1 MYOPYNHXINLPTK-UHFFFAOYSA-N 0.000 description 1
- MFXFQKMUCYHPFQ-BKRJIHRRSA-N 6-monoacetylcodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](OC(C)=O)[C@@H]1OC1=C2C3=CC=C1OC MFXFQKMUCYHPFQ-BKRJIHRRSA-N 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003855 acyl compounds Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000010411 cooking Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960002085 oxycodone Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von Acylderivaten der Enolform des Codeinons Es ist bekannt, daß das aus Codein durch Odxydation z. B. mit Chromsäure erhältliche Codeinon ebenso wie dessen Enolmethyläther, das Thebain, die sogenannte Morpholspaltung erleidet: Es wird beim Kochen mit Essigsäureanhydrid in ein neutrales Spaltstück, das 3-Methoxy-4, 6-diacetoxyphenanthren und Äthanolmethylamin gespalten (L. Knorr, Berichte der Deutschen Chem. Gesellschaft, Bd.36, S.3081 [19o3]).Process for the preparation of acyl derivatives of the enol form of codeinone It is known that the codeine by odxydation z. B. available with chromic acid Codeinone as well as its enol methyl ether, thebaine, the so-called morphol cleavage suffers: When cooking with acetic anhydride, it is cut into a neutral split piece, split the 3-methoxy-4, 6-diacetoxyphenanthrene and ethanolmethylamine (L. Knorr, Reports of the German Chemical Society, vol. 36, p. 3081 [19o3]).
Es wurde nun gefunden, daß man bei dieser Umsetzung eine Base, die offenbar ein Zwischenprodukt der Spaltungsreaktion ist, in guter Ausbeute dadurch fassen kann, daß man das Essigsäureanhydrid längere Zeit bei Zimmertemperatur oder nur wenig erhöhter Temperatur auf Codeinon einwirken läßt. Eine Abänderung des Verfahrens besteht darin, daß man die Einwirkung von Essigsäureanhydrid bei dessen Siedepunkt oder in dessen Nähe unterbricht, bevor die Morpholspaltung merklich geworden ist. Die Aufarbeitung kann dadurch erfolgen, daß man die Reaktionslösung zur Zersetzung des überschüssigen Anhydrids auf eine Soda-Eis-Mischung gießt und die abgeschiedene Base mit organischen Lösungsmitteln ausschüttelt. Oder man dampft die Reaktionsmischung bei niedriger Temperatur im Vakuum ein, nimmt den Rückstand in Wasser auf und macht mit Bicarbonat alkalisch. Die abgeschiedene Base wird mit Äther ausgeschüttelt und nach Verdampfen des Äthers in kristallisierter Form vom F. = 133 bis 13q.° erhalten.It has now been found that in this reaction, a base that apparently an intermediate product of the cleavage reaction, in good yield thereby can grasp that the acetic anhydride for a long time at room temperature or only lets the codeinone act at a slightly elevated temperature. A change in the procedure consists in being exposed to acetic anhydride at its boiling point or interrupts in the vicinity before the morphol cleavage has become noticeable. Working up can be carried out by allowing the reaction solution to decompose of the excess anhydride is poured onto a soda-ice mixture and the deposited Shakes out base with organic solvents. Or the reaction mixture is evaporated at low temperature in a vacuum, the residue is taken up in water and makes alkaline with bicarbonate. The deposited base is shaken out with ether and obtained after evaporation of the ether in crystallized form of F. = 133 to 13q. °.
Berechnet für C20 H2104 N: C 70,75°/0, H 6,24°/a; gefunden: C 70,62 0/0, H 6,29 0/0.Calculated for C20 H2104 N: C 70.75 ° / 0, H 6.24 ° / a; Found: C 70.62 0/0, H 6.29 0/0.
Die Analyse zeigt, daß das Codeinon eine Acetylgruppe aufgenommen hat. Die neue Verbindung gibt mit konzentrierten Säuren quantitativ dieselbe tieforangerote Halochromie wie das Thebain. Sie besitzt daher die Konstitution eines Enolacetats der Formel Die neue Verbindung kann denselben Umsetzungen des konjugierten Systems der Doppelbindungen unterworfen werden, denen auch Thebain zugänglich ist. So lagert sie z. B.an Doppelbindungen anlagerungsfähige Verbindungen wie Chinon oder Maleinsäureanhydrid an; mit Wasserstoffsuperoxyd wird sie zu Oxycodeinon oxydiert.The analysis shows that the codeinone has taken up an acetyl group. With concentrated acids, the new compound gives quantitatively the same deep orange-red halochromy as thebaine. It therefore has the constitution of an enol acetate of the formula The new compound can be subjected to the same reactions of the conjugated system of double bonds to which thebaine is also accessible. So she stores z. B. on double bonds attachable compounds such as quinone or maleic anhydride; with hydrogen peroxide it is oxidized to oxycodeinone.
Bei der erfindungsgemäßen Umsetzung können an Stelle von Essigsäureanhydrid flüssige Anhydride anderer niederer Fettsäuren verwandt werden, und man erhält die entsprechenden Acylverbindungen.In the reaction according to the invention, instead of acetic anhydride liquid anhydrides of other lower fatty acids are used, and one obtains the corresponding acyl compounds.
Beispiel 3 g Codeinon vom F. = 18o bis 181° werden mit 15 g frisch destilliertem Essigsäureanhydrid zwei Tage bei Zimmertemperatur geschüttelt, wobei das zunächst suspendierte Codeinon in Lösung geht. Man dampft bei Zimmertemperatur im Vakuum das überschüssige Essigsäureanhydrid ab und verreibt den harzigen Rückstand mit wasserfreiem Äther, wobei sich das Acetat des Codeinonenolacetats als mikrokristallines, bräunlich verfärbtes, leicht absaugbares Pulver abscheidet. Man saugt ab und wäscht mit Äther nach. Durch Umkristallisieren aus Essigester erhält man das Acetat in farblosen Kristallen vom F. = 104 bis i05°.Example 3 g of codeinone with a temperature of 18o to 181 ° are fresh with 15 g distilled acetic anhydride shaken for two days at room temperature, whereby the initially suspended codeinone goes into solution. Steam at room temperature the excess acetic anhydride is removed in vacuo and the resinous residue is rubbed off with anhydrous ether, whereby the acetate of codeinone olacetate is a microcrystalline, A brownish discolored powder that can be easily extracted is deposited. You vacuum and wash with ether after. Recrystallization from ethyl acetate gives the acetate in colorless crystals from m.p. 104 to 105 °.
Das Acetat wird in wenig eiskaltem Wasser gelöst, die Lösung mit Bicarbonat versetzt und die abgeschiedene Base mit viel peroxydfreiem Äther aufgenommen, wobei eine kleine Menge amorpher Flocken ungelöst bleibt. Man trocknet den Äther über Natriumsulfat, versetzt mit wenig Aktivkohle, filtriert und dampft die Ätherlösung auf dem Wasserbad ein. Das Codeinonenolacetat bleibt als Harz zurück, das nach einiger Zeit strahlig zu Kristallen erstarrt. Ausbeute 1,9 g. Durch Umkristallisieren aus Hexan, in dem ein kleiner Teil des Rohprodukts unlöslich ist, wird die Base mit dem scharfen Schmelzpunkt 133 bis i34° erhalten. Mit dem bei der gleichen Temperatur schmelzenden Acetylcodein gibt die Verbindung eine starke Schmelzpunktserniedrigung.The acetate is dissolved in a little ice-cold water, the solution with bicarbonate added and the deposited base was added with plenty of peroxide-free ether, with a small amount of amorphous flakes remains undissolved. The ether is dried over Sodium sulfate, mixed with a little activated charcoal, filtered and evaporated the ethereal solution on the water bath. The codeine enol acetate remains as a resin, which after some Time solidified radiantly to crystals. Yield 1.9g. By recrystallization Hexane, in which a small part of the crude product is insoluble, becomes the base with the sharp melting point of 133-134 °. With that at the same temperature melting acetylcodeine gives the compound a strong lowering of the melting point.
Die neue Verbindung zeigt wie Thebain intensive Halochromie mit konzentrierter Schwefelsäure und konzentrierter Salzsäure. Das Pikrat der Base wird durch Lösen derselben in verdünnter Essigsäure und Fällung mit wäßriger Pikrinsäure erhalten. Das zunächst amorph ausfallende Pikrat wird abgesaugt, getrocknet und bei Zimmertemperatur in Methanol gelöst, aus dem beim Einengen im Vakuum zunächst amorphe Anteile ausfallen, von denen abgesaugt wird. Beim weiteren Einengen der Methanollösung kristallisiert das Pikrat des Codeinonenolacetats aus, das nach zweimaligem Umkristallisieren durch Einengen der bei Zimmertemperatur bereiteten Methanollösung in Prismen vom F. = toi bis 2o3° unter Zersetzung erhalten wird. Mit dem bei i97° unter Zersetzung schmelzenden Codeinonpikrat gibt es eine starke Schmelzpunktserniedrigung auf 184 bis 188°.Like thebaine, the new compound shows intense halochromy with more concentrated Sulfuric acid and concentrated hydrochloric acid. The picrate of the base is obtained by dissolving the same obtained in dilute acetic acid and precipitation with aqueous picric acid. The picrate, which initially precipitates amorphously, is filtered off with suction, dried and at room temperature dissolved in methanol, from which amorphous fractions initially precipitate when concentrated in vacuo, from which is sucked off. When the methanol solution is concentrated further, it crystallizes the picrate of Codeinonenolacetats, which after recrystallizing twice Concentration of the methanol solution prepared at room temperature in prisms from F. = toi is obtained up to 2o3 ° with decomposition. With the melting point at 97 ° with decomposition Codeinone picrate there is a strong depression of the melting point to 184 to 188 °.
Analyse: C2oHg104N - C,H307N3 (568,5). Berechnet: C 54,90%, H 4,250/0, N 9,85%; gefunden: C 54,76 0/0, H 4,23 0/0, N 9,77 %-Das Pikrat gibt im Gegensatz zu Codeinonpikrat intensive orangerote Halochromie mit konzentrierter Schwefelsäure und konzentrierter Salzsäure.Analysis: C2oHg104N-C, H307N3 (568.5). Calculated: C 54.90%, H 4.250 / 0, N 9.85%; found: C 54.76 0/0, H 4.23 0/0, N 9.77% -The picrate gives in contrast to codeinone picrate, intense orange-red halochromy with concentrated sulfuric acid and concentrated hydrochloric acid.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK10625A DE902257C (en) | 1951-07-17 | 1951-07-17 | Process for the preparation of acyl derivatives of the enol form of codeinone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEK10625A DE902257C (en) | 1951-07-17 | 1951-07-17 | Process for the preparation of acyl derivatives of the enol form of codeinone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE902257C true DE902257C (en) | 1954-01-21 |
Family
ID=7212965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEK10625A Expired DE902257C (en) | 1951-07-17 | 1951-07-17 | Process for the preparation of acyl derivatives of the enol form of codeinone |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE902257C (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2515184A1 (en) * | 1981-08-17 | 1983-04-29 | Univ Florida State | SYNTHESES OF CODEINE DERIVATIVES AND OTHER 3-O-ALKYLMORPHINS AND INTERMEDIATE COMPOUNDS USED THEREOF |
| US4795813A (en) * | 1981-08-17 | 1989-01-03 | The Florida Board Of Regents On Behalf Of The Florida State University | Synthesis of derivatives of codeine and other 3-O-alkylmorphines |
| EP0889045A1 (en) * | 1997-06-30 | 1999-01-07 | Johnson Matthey Public Limited Company | Process for the production of thebaine and analogues thereof, as well as intermediate products therefor |
| US8003793B2 (en) | 2004-02-06 | 2011-08-23 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
-
1951
- 1951-07-17 DE DEK10625A patent/DE902257C/en not_active Expired
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2515184A1 (en) * | 1981-08-17 | 1983-04-29 | Univ Florida State | SYNTHESES OF CODEINE DERIVATIVES AND OTHER 3-O-ALKYLMORPHINS AND INTERMEDIATE COMPOUNDS USED THEREOF |
| US4795813A (en) * | 1981-08-17 | 1989-01-03 | The Florida Board Of Regents On Behalf Of The Florida State University | Synthesis of derivatives of codeine and other 3-O-alkylmorphines |
| EP0889045A1 (en) * | 1997-06-30 | 1999-01-07 | Johnson Matthey Public Limited Company | Process for the production of thebaine and analogues thereof, as well as intermediate products therefor |
| US6090943A (en) * | 1997-06-30 | 2000-07-18 | Johnson Matthey Public Limited Company | Preparation of opiates, intermediates and uses of salts |
| US6365742B1 (en) | 1997-06-30 | 2002-04-02 | Johnson Matthey Public Limited Company | Preparation of opiates, intermediates and uses of salts |
| US8003793B2 (en) | 2004-02-06 | 2011-08-23 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
| US8198444B2 (en) | 2004-02-06 | 2012-06-12 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
| US8685996B2 (en) | 2004-02-06 | 2014-04-01 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
| US8975257B2 (en) | 2004-02-06 | 2015-03-10 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
| US9670218B2 (en) | 2004-02-06 | 2017-06-06 | Purdue Pharma L.P. | Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates |
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