CH298416A - Process for the preparation of (+) - 3-methoxy-N-methyl-morphinan. - Google Patents
Process for the preparation of (+) - 3-methoxy-N-methyl-morphinan.Info
- Publication number
- CH298416A CH298416A CH298416DA CH298416A CH 298416 A CH298416 A CH 298416A CH 298416D A CH298416D A CH 298416DA CH 298416 A CH298416 A CH 298416A
- Authority
- CH
- Switzerland
- Prior art keywords
- sep
- methyl
- methoxy
- morphinan
- melting point
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 6
- MKXZASYAUGDDCJ-NJAFHUGGSA-N dextromethorphan Chemical compound C([C@@H]12)CCC[C@]11CCN(C)[C@H]2CC2=CC=C(OC)C=C21 MKXZASYAUGDDCJ-NJAFHUGGSA-N 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 2
- 238000002844 melting Methods 0.000 claims description 7
- 230000008018 melting Effects 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 239000012022 methylating agents Substances 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 2
- HADKRTWCOYPCPH-UHFFFAOYSA-M trimethylphenylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C1=CC=CC=C1 HADKRTWCOYPCPH-UHFFFAOYSA-M 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical compound C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- LDZLXQFDGRCELX-UHFFFAOYSA-N 4-phenylbutan-1-ol Chemical compound OCCCCC1=CC=CC=C1 LDZLXQFDGRCELX-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- MKXZASYAUGDDCJ-CGTJXYLNSA-N levomethorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(C)[C@@H]2CC2=CC=C(OC)C=C21 MKXZASYAUGDDCJ-CGTJXYLNSA-N 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- BKBMACKZOSMMGT-UHFFFAOYSA-N methanol;toluene Chemical compound OC.CC1=CC=CC=C1 BKBMACKZOSMMGT-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- MQAYPFVXSPHGJM-UHFFFAOYSA-M trimethyl(phenyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)C1=CC=CC=C1 MQAYPFVXSPHGJM-UHFFFAOYSA-M 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung von (+)-3-Methoxy-N-methyl-morphinan. Gegenstand des Patentes ist ein Verfahren zur Herstellung von (+ ) -3-Methoxy-N-methyl- morphinän, welches dadurch gekennzeichnet ist, dass man (+) -3-Oxy-N-methyl-morphinan mit einem Methylierungsmittel behandelt.
Als Methylierungsmittel wird vorzugs weise Phenyl-trimethyl-ammonium-hydroxyd verwendet.
Das Ausgangsmaterial für das erfindungs gemässe Verfahren kann zum Beispiel dadurch gewonnen werden, dass man eine wässerige Lösung von (+)-3-Oxy-N-methyl-morphinan- tartrat schwach alkalisch stellt und die ent standene freie Base mit einem Benzol-Buta- nol-Gemischextrahiert.
Die neue Verbindung zeigt interessante pharmakologische Eigenschaften und soll als Heilmittel verwendet werden.
<I>Beispiel:</I> 21,2 Gewichtsteile (-I- )-3-Oxy-N-methyl- morphinan-tartrat werden in Wasser warm gelöst. Die Lösung wird mit Ammoniak schwach alkalisch gestellt und die (+ )-Base mit Benzol-Butanol-Gemisch <B>(1:1)</B> ausge schüttelt.
Nach Abdestillieren des Lösungs mittels wird der Rückstand in 400 Raumtei len Toluol aufgenommen; sodann werden 125 Raumteile Toluol abdestilliert. Zu der so er- haltenen.trockenen Lösung wird die folgender massen hergestellte Methylierungslauge bei 20 C zugefügt.
' 17,2 Gewichtsteile Phenyl-trimethyl-ammo- niumchlorid werden in 25 Raumteilen Metha- nol gelöst und bei 25 C eine aus 2,25 Ge wichtsteilen Natrium und 25 Raumteilen Me thanol bereitete Lösung zugegeben: Das dabei auftretende Natriumchlorid wird unter Feuch- tigkeits- und Kohlensäureausachluss abfiltriert.
Die Lösung der (+)-Base und die Methy- lierungslauge werden unter Rühren erwärmt, so dass zuerst Methanol, dann ein Methanol- Toluol-Gemisch und schliesslich Toluol allein abdestilliert. Die Reaktionslösung wird nach dem Abkühlen mit eiskalter, verdünnter Na tronlauge gewaschen. Aus der Toluollösung wird das (+) -3-Methoxy-N-methyl-morphinan mit verdünnter Bromwasserstoffsäure ausge zogen und kristallisiert.
Schmelzpunkt des Hydrobromides 124-126 C. [a] = + 26,3 D (c = 1,5 in Wasser).
Aus. der wässerigen Lösung des Hydro- bromides kann mit verdünntem Ammoniak die freie Base vom Schmelzpunkt 108-111 C und [a] D = +49,3 (c = 1,5 in absolutem Alkohol), und daraus das Tartrat vom Schmelzpunkt 195-196 C, [a] D = + 30,6 (c = 1,5 in Wasser) hergestellt werden. Schmelzpunkt des Hydrojodides 125-127 C, des Methojodides 239-240 C. .
Process for the preparation of (+) - 3-methoxy-N-methyl-morphinan. The subject of the patent is a process for the production of (+) -3-methoxy-N-methyl-morphinane, which is characterized in that (+) -3-oxy-N-methyl-morphinane is treated with a methylating agent.
Phenyltrimethylammonium hydroxide is preferably used as the methylating agent.
The starting material for the process according to the invention can be obtained, for example, by making an aqueous solution of (+) - 3-oxy-N-methyl-morphine tartrate slightly alkaline and treating the resulting free base with a benzene-buta nol mixtures extracted.
The new compound shows interesting pharmacological properties and is said to be used as a medicine.
<I> Example: </I> 21.2 parts by weight of (-I-) -3-oxy-N-methylmorphinan tartrate are dissolved in warm water. The solution is made slightly alkaline with ammonia and the (+) base is shaken out with a benzene-butanol mixture <B> (1: 1) </B>.
After the solvent has been distilled off, the residue is taken up in 400 parts of toluene; 125 parts by volume of toluene are then distilled off. The methylation liquor prepared in the following manner is added at 20 ° C. to the dry solution obtained in this way.
17.2 parts by weight of phenyl-trimethyl-ammonium chloride are dissolved in 25 parts by volume of methanol and a solution made up of 2.25 parts by weight of sodium and 25 parts by volume of methanol is added at 25 ° C. The sodium chloride that occurs is dissolved under moisture - and the discharge of carbonic acid filtered off.
The solution of the (+) base and the methylation liquor are heated with stirring so that first methanol, then a methanol-toluene mixture and finally toluene alone is distilled off. After cooling, the reaction solution is washed with ice-cold, dilute sodium hydroxide solution. The (+) -3-methoxy-N-methyl-morphinane is extracted from the toluene solution with dilute hydrobromic acid and crystallized.
Melting point of the hydrobromide 124-126 C. [a] = + 26.3 D (c = 1.5 in water).
Out. the aqueous solution of the hydrobromide can with dilute ammonia the free base with a melting point of 108-111 C and [a] D = +49.3 (c = 1.5 in absolute alcohol), and from it the tartrate with a melting point of 195-196 C, [a] D = + 30.6 (c = 1.5 in water). Melting point of the Hydroiodide 125-127 C, of the Methojodide 239-240 C..
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH298416T | 1950-09-15 | ||
| CH293812T | 1950-09-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH298416A true CH298416A (en) | 1954-04-30 |
Family
ID=25733435
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH298416D CH298416A (en) | 1950-09-15 | 1950-09-15 | Process for the preparation of (+) - 3-methoxy-N-methyl-morphinan. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH298416A (en) |
-
1950
- 1950-09-15 CH CH298416D patent/CH298416A/en unknown
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