CH340823A - Process for the preparation of a benzamido-phenyl-piperidino-propane - Google Patents
Process for the preparation of a benzamido-phenyl-piperidino-propaneInfo
- Publication number
- CH340823A CH340823A CH340823DA CH340823A CH 340823 A CH340823 A CH 340823A CH 340823D A CH340823D A CH 340823DA CH 340823 A CH340823 A CH 340823A
- Authority
- CH
- Switzerland
- Prior art keywords
- piperidino
- phenyl
- methyl
- benzamido
- propane
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 3
- QCWXSLAYNPTSKI-UHFFFAOYSA-N CCC(C1=CC=CC=C1)(NC(C1=CC=CC=C1)=O)N1CCCCC1 Chemical compound CCC(C1=CC=CC=C1)(NC(C1=CC=CC=C1)=O)N1CCCCC1 QCWXSLAYNPTSKI-UHFFFAOYSA-N 0.000 title description 2
- -1 1-phenyl-2-methyl-3-piperidino- propylamine Chemical compound 0.000 claims description 7
- YJNFZIRUSJRKOH-UHFFFAOYSA-N C(C1=CC=CC=C1)(=O)NC(C(CN1CCCCC1)C)C1=CC=CC=C1 Chemical compound C(C1=CC=CC=C1)(=O)NC(C(CN1CCCCC1)C)C1=CC=CC=C1 YJNFZIRUSJRKOH-UHFFFAOYSA-N 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
<Desc/Clms Page number 1>
Verfahren zur Herstellung eines Benzamido-phenyl-piperidino-propans Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung einer neuen Verbindung, nämlich des 1-Benzamido-1-phenyl-2-methyl-3-piperidino- propans, der Formel:
EMI1.4
welche dadurch erhalten wird, dass man a-Methyl-ss- piperidino-propiophenon mit Hydroxylamin umsetzt, das erhaltene a-Methyl-,B-piperidino-propiophenon- oxim unter Bildung von 1-Phenyl-2-methyl-3-piperi- dino-propylamin hydriert, das erhaltene Amin mit Benzoylehlorid umsetzt und das anfallende Hydro- chlorid in das 1-Benzamido-l-phenyl-2-methyl-3-pi- peridino-propan überführt.
Die neue Verbindung stellt eine kristalline Substanz vom Schmelzpunkt von 115-116 C dar, ist in Wasser verhältnismässig unlöslich, jedoch in den üblichen polaren organischen Lösungsmitteln löslich.
Die neue Verbindung ist ein lokales Anästhetikum, das sich durch Beständigkeit, Abwesenheit von irgendwelchen Reizerscheinungen bei dessen Applikation und durch langanhaltende Wirkung auszeichnet. Für therapeutische Zwecke wird man die neue Verbindung vorteilhafterweise als wässrige Lösung ihres sauren Additionssalzes anwenden, oder die freie Base kann in verschiedene pharmazeutische Streckmedien, wie z. B. Salben, Gele, Öle, Lotionen, suspendierenden Medien und dergleichen, einverleibt werden.
Beispiel v-Methyl-,ss-piperidino-propionphenon, erhalten nach der Methode von Ruddy, Z. A. C. B. 72, 718 (1950), wird mit Hydroxylamin unter Bildung von a-Methyl-ss-piperidino-propiophenonoxim kondensiert. Das Oxim wird dann nach den im Beispiel des Hauptpatentes gemachten Angaben mittels Raney- Nickel zum 1-Phenyl-2-methyl-3-piperidino-propyl- amin reduziert. Diese letztere Verbindung siedet bei einem Druck von 0,5 mm Hg bei 128-129 C. Der Refraktionsindex bei 25 C beträgt 1,5250.
Analyse: Berechnet für C15Hz4Nz0: N 12,06 Gefunden: N 12,18 Ein Gemisch von 9,7 g 1-Phenyl-2-methyl-3-piperi- dino-propylamin, 9,7 cm3 Benzoylchlorid, 20 cm3 trockenem Pyridin und 100 cm3 Benzol wird während etwa 16 Stunden bei Zimmertemperatur stehengelassen. Hierauf versetzt man das Reaktionsgemisch mit einer genügenden Menge an Äthyläther, um eine vollständige Ausfällung des während der Umsetzung entstandenen 1-Benzamido-1-phenyl-2-methyl-3-pi- peridino-propan-hydrochlorids zu bewirken. Der Niederschlag wird abgetrennt.
Nach dem Umkristallisie- ren aus einem Gemisch von Äthylacetat und Methanol schmilzt das erhaltene 1-Benzamido-l-phenyl-2- methyl-3-piperidino-propan-hydrochlorid bei 262 bis 263 C.
<Desc/Clms Page number 2>
Analyse: Berechnet für C22HzsN20C1: N 7,51 Cl 9,51 Gefunden: N 7,46 Cl 9,40 50 g des 1-Benzamido-l-phenyl-2-methyl-3-pi- peridino-propan-hydrochlorids werden mit 200 cm3 Äther und 200 cm3 verdünntem, wässrigem Ammo- niumhydroxyd geschüttelt.
Die die freie Base enthaltende Ätherschicht wird über wasserfreiem Magne- siumsulfat getrocknet und der Äther durch Destillation entfernt. Der Rückstand wird in ungefähr 100 cm?- heissem Äthylacetat gelöst und so lange mit Petroläther versetzt, bis Kristallisation eintritt. Der kristalline Niederschlag, bestehend aus 1-Benzamido- 1-phenyl-2-methyl-3-piperidino-propan schmilzt nach dem Umkristallisieren aus einem Gemisch aus Athyl- acetat und Petroläther bei etwa 115-116 C.
Analyse: Berechnet für C2A.N20: N 8,33 % Gefunden: N 8,30 %
<Desc / Clms Page number 1>
Process for the preparation of a benzamido-phenyl-piperidino-propane The present invention relates to a process for the preparation of a new compound, namely 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane, of the formula:
EMI1.4
which is obtained by reacting a-methyl-ss-piperidino-propiophenone with hydroxylamine, the resulting a-methyl-, B-piperidino-propiophenone oxime to form 1-phenyl-2-methyl-3-piperidino -propylamine is hydrogenated, the amine obtained is reacted with benzoyle chloride and the hydrochloride obtained is converted into 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane.
The new compound is a crystalline substance with a melting point of 115-116 C, is relatively insoluble in water, but soluble in the usual polar organic solvents.
The new compound is a local anesthetic that is characterized by durability, the absence of any irritation when it is applied and a long-lasting effect. For therapeutic purposes, the new compound is advantageously used as an aqueous solution of its acidic addition salt, or the free base can be added to various pharmaceutical diluent media, such as. B. ointments, gels, oils, lotions, suspending media and the like can be incorporated.
Example v-methyl-, ss-piperidino-propionphenone, obtained by the method of Ruddy, Z.A.C.B. 72, 718 (1950), is condensed with hydroxylamine to form α-methyl-ss-piperidino-propiophenone oxime. The oxime is then reduced to 1-phenyl-2-methyl-3-piperidino-propylamine using Raney nickel according to the information given in the example of the main patent. This latter compound boils at 128-129 C at a pressure of 0.5 mm Hg. The refractive index at 25 C is 1.5250.
Analysis: Calculated for C15Hz4Nz0: N 12.06 Found: N 12.18 A mixture of 9.7 g of 1-phenyl-2-methyl-3-piperidino-propylamine, 9.7 cm 3 of benzoyl chloride, 20 cm 3 of dry pyridine and 100 cm3 of benzene is left to stand for about 16 hours at room temperature. A sufficient amount of ethyl ether is then added to the reaction mixture to bring about complete precipitation of the 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane hydrochloride formed during the reaction. The precipitate is separated off.
After recrystallization from a mixture of ethyl acetate and methanol, the 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane hydrochloride obtained melts at 262 to 263 C.
<Desc / Clms Page number 2>
Analysis: Calculated for C22HzsN20C1: N 7.51 Cl 9.51 Found: N 7.46 Cl 9.40 50 g of 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane hydrochloride are added 200 cm3 of ether and 200 cm3 of diluted, aqueous ammonium hydroxide are shaken.
The ether layer containing the free base is dried over anhydrous magnesium sulfate and the ether is removed by distillation. The residue is dissolved in about 100 cm? - hot ethyl acetate and petroleum ether is added until crystallization occurs. The crystalline precipitate, consisting of 1-benzamido-1-phenyl-2-methyl-3-piperidino-propane, melts after recrystallization from a mixture of ethyl acetate and petroleum ether at about 115-116 C.
Analysis: Calculated for C2A.N20: N 8.33% Found: N 8.30%
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US322062XA | 1952-11-10 | 1952-11-10 | |
| US340823XA | 1952-11-10 | 1952-11-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH340823A true CH340823A (en) | 1959-09-15 |
Family
ID=32929807
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH340823D CH340823A (en) | 1952-11-10 | 1953-10-13 | Process for the preparation of a benzamido-phenyl-piperidino-propane |
| CH322062D CH322062A (en) | 1952-11-10 | 1953-10-13 | Process for the preparation of a benzamido-phenyl-piperidinopropane |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH322062D CH322062A (en) | 1952-11-10 | 1953-10-13 | Process for the preparation of a benzamido-phenyl-piperidinopropane |
Country Status (1)
| Country | Link |
|---|---|
| CH (2) | CH340823A (en) |
-
1953
- 1953-10-13 CH CH340823D patent/CH340823A/en unknown
- 1953-10-13 CH CH322062D patent/CH322062A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CH322062A (en) | 1957-05-31 |
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