DE1162847B - Process for the preparation of N-diphenylalkyl-norgranatane and -nortropane derivatives. - Google Patents
Process for the preparation of N-diphenylalkyl-norgranatane and -nortropane derivatives.Info
- Publication number
- DE1162847B DE1162847B DE1962B0065780 DEB0065780A DE1162847B DE 1162847 B DE1162847 B DE 1162847B DE 1962B0065780 DE1962B0065780 DE 1962B0065780 DE B0065780 A DEB0065780 A DE B0065780A DE 1162847 B DE1162847 B DE 1162847B
- Authority
- DE
- Germany
- Prior art keywords
- nortropane
- norgranatane
- derivatives
- diphenyl
- formula
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 7
- 238000002360 preparation method Methods 0.000 title claims description 3
- OXTNCQMOKLOUAM-UHFFFAOYSA-N 3-Oxoglutaric acid Chemical compound OC(=O)CC(=O)CC(O)=O OXTNCQMOKLOUAM-UHFFFAOYSA-N 0.000 claims description 4
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 claims description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 2
- PCSMJKASWLYICJ-UHFFFAOYSA-N Succinic aldehyde Chemical compound O=CCCC=O PCSMJKASWLYICJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910001854 alkali hydroxide Inorganic materials 0.000 claims description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- -1 phenyl magnesium halides Chemical class 0.000 claims description 2
- 150000008303 tropinone derivatives Chemical class 0.000 claims description 2
- 230000007246 mechanism Effects 0.000 claims 1
- RHWSKVCZXBAWLZ-OCAPTIKFSA-N pseudopelletierine Chemical compound C1CC[C@@H]2CC(=O)C[C@H]1N2C RHWSKVCZXBAWLZ-OCAPTIKFSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 239000000155 melt Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000000954 anitussive effect Effects 0.000 description 2
- 239000003434 antitussive agent Substances 0.000 description 2
- 229940124584 antitussives Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WPDWOCRJBPXJFM-UHFFFAOYSA-N 2-bromo-1-phenylpropan-1-one Chemical compound CC(Br)C(=O)C1=CC=CC=C1 WPDWOCRJBPXJFM-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- KRIOVPPHQSLHCZ-UHFFFAOYSA-N propiophenone Chemical compound CCC(=O)C1=CC=CC=C1 KRIOVPPHQSLHCZ-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY
DEUTSCHESGERMAN
PATENTAMTPATENT OFFICE
AUSLEGESCHRIFTEDITORIAL
Internat. Kl.: C07d Boarding school Class: C07d
Nummer:
Aktenzeichen:
Anmeldetag:
Auslegetag:Number:
File number:
Registration date:
Display day:
Deutsche Kl.: 12 ρ-13German class: 12 ρ-13
B 65780 IVd/12 ρ
2. Februar 1962
13. Februar 1964B 65780 IVd / 12 ρ
2nd February 1962
February 13, 1964
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von N-Diphenylalkyl-norgranatan- und -nortropan-Derivaten der allgemeinen FormellThe invention relates to a process for the preparation of N-diphenylalkyl-norgranatan- and -nortropane derivatives of the general formula
(C6Hs)2C-Z(C 6 Hs) 2 CZ
-V A-V A
(CHa).(CHa).
(I)(I)
in der X ein Wasserstoffatom oder die Hydroxylgruppe darstellt, η die Zahl 2 oder 3 bedeutet und Z Alkylreste mit 1 bis 4 Kohlenstoffatomen darstellt, das dadurch gekennzeichnet ist, daß man in an sich bekannter Weise Amine der Formelin which X represents a hydrogen atom or the hydroxyl group, η represents the number 2 or 3 and Z represents alkyl radicals having 1 to 4 carbon atoms, which is characterized in that amines of the formula
(C6Hs)2C-Z-NH2 (C 6 Hs) 2 CZ-NH 2
mit Acetondicarbonsäure und Glutardialdehyd bzw. Succindialdehyd umsetzt, und die erhaltenen Pseudopelletierin- bzw. Tropinonderivate mit Hydrazinhydrat und Alkalihydroxyd behandelt oder zur Herstellung von 1,1-Diphenyl-1-hydroxyalkyl-norgranatanen bzw. -nortropanen Halogenketone der Formelwith acetone dicarboxylic acid and glutaraldehyde or succinic dialdehyde, and the resulting pseudopelletierin- or tropinone derivatives treated with hydrazine hydrate and alkali hydroxide or for the production of 1,1-diphenyl-1-hydroxyalkyl-norgranatanes or -nortropane halogen ketones of the formula
C6H5CO-Z-HaIC 6 H 5 CO-Z-Hal
in der Hai Halogenatome darstellt, mit Norgranatan bzw. Nortropan umsetzt und die erhaltenen N-Benzoylalkyl-norgranatane bzw. -nortropane mit Phenylmagnesiumhalogeniden behandelt.in which Hai represents halogen atoms, reacts with norgranatane or nortropane and the resulting N-benzoylalkyl-norgranatane or -nortropane treated with phenylmagnesium halides.
Die verfahrensgemäß hergestellten Verbindungen sind hervorragende Antitussiva, die bekannten Mitteln der gleichen Wirkungsrichtung überlegen sind. Im Vergleich zu dem als Hustenmittel z. B. aus der deutschen Patentschrift 1021 846 bekannten N- [ 1,1 -Diphenyl-1 -hydroxy-propyl-(2)]-piperidin ist z. B. die entsprechende Norgranatan verbindung (Beispiel 3) bedeutend weniger toxisch, so daß sie — bei gleich starker antitussiver Wirkung — eine größere therapeutische Breite besitzt.The compounds prepared according to the process are excellent antitussives, the known agents are superior in the same direction of action. Compared to the cough suppressant z. B. off the German patent 1021 846 known N- [1,1 -diphenyl-1-hydroxy-propyl- (2)] - piperidine z. B. the corresponding Norgranatan compound (Example 3) significantly less toxic, so that they - at equally strong antitussive effect - has a greater therapeutic range.
In den folgenden Beispielen wird das erfindungsgemäße Verfahren erläutert.The process according to the invention is illustrated in the following examples.
1. N-[l,l-Diphenyl-l-hydroxy-propyl-(3)]-norgranatan 1. N- [1,1-Diphenyl-1-hydroxypropyl- (3)] - norgranatan
Verfahren zur Herstellung von N-Diphenylalkylnorgranatan- und -nortropan-DerivatenProcess for the production of N-Diphenylalkylnorgranatan- and -nortropane derivatives
Anmelder:Applicant:
C. F. Boehringer & Soehne G. m. b. H.,C. F. Boehringer & Soehne G. m. B. H.,
Mannheim-WaldhofMannheim-Waldhof
Als Erfinder benannt:Named as inventor:
Dr.-Ing. Kurt Stach, Mannheim,Dr.-Ing. Kurt Stach, Mannheim,
Dr. rer. nat. Otto DoId, Lampertheim (Hess.),Dr. rer. nat. Otto DoId, Lampertheim (Hess.),
Dr. med. Wolfgang Schaumann,Dr. med. Wolfgang Schaumann,
Mannheim-WaldhofMannheim-Waldhof
25%ige Glutardialdehydlösung und 30 g Natriumacetat (Trihydrat) zugesetzt; der pH-Wert wird auf 3,5 eingestellt und der Ansatz 4 Tage bei Zimmertemperatur stehengelassen. Nach dieser Zeit können 83,6 g des inzwischen kristallin ausgefallenen N- [1,1 -Diphenyl-1 -hydroxy-propyl-(3)]-norpseudopelletierin-hydrochlorids abgesaugt werden; die Rohausbeute beträgt 86,6%. Das Salz schmilzt nach dem Umkristallisieren aus Alkohol unter Zusatz von Wasser bei 256°C (unter Zersetzung). Aus einer Lösung des Salzes in Wasser erhält man durch Zugeben von Natronlauge die in fester Form ausfallende Base; F. 142 bis 144°C (aus Petroläther). b) 15,5 g N-[1,1 -Diphenyl-l-hydroxy-propyl-(3)]-norpseudppelletierin, 33 ml Hydrazinhydrat, 5 ml Wasser, 33 g Kaliumhydroxyd und 200 ml Triglycol werden unter Rühren langsam auf 2500C erhitzt und dabei übergehende leicht flüchtige Substanzen an einem absteigenden Kühler kondensiert. Nach dem etwa 2stündigen Erhitzen läßt man das Reaktionsgemisch abkühlen, versetzt mit Wasser und extrahiert mit Chloroform. Der Extrakt wird getrocknet, eingeengt und der Rückstand aus Alkohol umkristallisiert. Man erhält 11,2 g N-[1,1 -Diphenyl- l-hydroxy-propyl-(3)]-norgranatan vom F. 97 bis 99°C; die Ausbeute beträgt 75,3%. Das Hydrochlorid schmilzt nach der Umkristallisation aus Alkohol und wenig Wasser bei 274° C (unter Zersetzung). 25% strength glutaraldehyde solution and 30 g sodium acetate (trihydrate) added; the pH is adjusted to 3.5 and the batch is left to stand for 4 days at room temperature. After this time, 83.6 g of the N- [1,1 -diphenyl-1-hydroxypropyl (3)] norpseudopelletierin hydrochloride, which has now precipitated in crystalline form, can be suctioned off; the gross yield is 86.6%. The salt melts after recrystallization from alcohol with the addition of water at 256 ° C (with decomposition). The base which precipitates out in solid form is obtained from a solution of the salt in water by adding sodium hydroxide solution; F. 142 to 144 ° C (from petroleum ether). b) 15.5 g of N- [1,1-diphenyl-l-hydroxy-propyl (3)] - norpseudppelletierin, 33 ml of hydrazine hydrate, 5 ml of water, 33 g of potassium hydroxide and 200 ml triglycol be added slowly with stirring to 250 0 C. and volatile substances passing over condensed on a descending cooler. After heating for about 2 hours, the reaction mixture is allowed to cool, water is added and the mixture is extracted with chloroform. The extract is dried and concentrated and the residue is recrystallized from alcohol. 11.2 g of N- [1,1-diphenyl-1-hydroxypropyl- (3)] -norgranatan with a melting point of 97 ° to 99 ° C. are obtained; the yield is 75.3%. After recrystallization from alcohol and a little water, the hydrochloride melts at 274 ° C. (with decomposition).
z. N-[l,l-Diphenyl-propyl-(3)]-norgranatanz. N- [1,1-diphenyl-propyl- (3)] -norgranatane
a) 57 g (0,25 Mol) 1,1-Diphenyl-1-hydroxy-propyl- 50 a) 31,7 g l,l-Diphenyl-propylamin-(3), 22 g amin-(3) werden in 42ml 6n-Salzsäure und 650ml Acetondicarbonsäure, 60ml 25%ige Glutardialde-Wasser gelöst und 44 g Acetondicarbonsäure, 120 ml hydlösung und 8,4 g Natriumacetat (Trihydrat)a) 57 g (0.25 mol) 1,1-diphenyl-1-hydroxypropyl-50 a) 31.7 g 1,1-diphenyl-propylamine- (3), 22 g amine- (3) are dissolved in 42ml 6N hydrochloric acid and 650ml acetone dicarboxylic acid, 60ml 25% glutardialde water dissolved and 44 g acetone dicarboxylic acid, 120 ml hyd solution and 8.4 g sodium acetate (trihydrate)
409 508/437409 508/437
werden in 375 ml Wasser gelöst und der pH-Wert auf 3,5 eingestellt. Nach 3tägigem Stehen bei Zimmertemperatur wird der Ansatz mit Natronlauge alkalisch gemacht und mehrmals mit Chloroform extrahiert. Die vereinigten Extrakte werden getrocknet, eingeengt und der schmierige Rückstand aus Essigester umkristallisiert. Man erhält 19,0 g N - [1,1 - Diphenyl - propyl - (3)] - norpseudopelletierin; die Ausbeute beträgt 38,0%. Nach dreimaligem Umkristallisieren schmilzt die Substanz bei 193 bis 195°C. Hydrochlorid: F.243°C unter Zersetzung (aus Alkohol und wenig Wasser).are dissolved in 375 ml of water and the pH is adjusted to 3.5. After 3 days of standing at At room temperature, the batch is made alkaline with sodium hydroxide solution and several times with chloroform extracted. The combined extracts are dried, concentrated and the greasy residue recrystallized from ethyl acetate. 19.0 g of N - [1,1 - diphenyl - propyl - (3)] - norpseudopelletierin are obtained; the yield is 38.0%. After three recrystallizations, the substance melts at 193 up to 195 ° C. Hydrochloride: F.243 ° C with decomposition (from alcohol and a little water).
b) Nach der im Beispiel 1, b) beschriebenen Arbeitsweise erhält man aus N-[l,l-Diphenyl-propyl-(3)]-norpseudopelletierin in 40,8%iger Ausbeute das N-[l,l-Diphenyl-propyl-(3)]-norgranatan vom F. 128 bis 1300C; die Substanz läßt sich aus Petroläther vom Kp. 100 bis 1400C Umkristallisieren. Das Hydrochlorid hat den Schmelzpunkt von 278 bis 280° C (aus Alkohol und etwas Wasser).b) Following the procedure described in Example 1, b), N- [l, l-diphenyl-propyl- (3)] - norpseudopelletierin is obtained in 40.8% yield of N- [l, l-diphenyl-propyl - (3)] - norgranatan from mp 128 to 130 0 C; the substance can be derived from petroleum ether, bp. 100 to 140 0 C recrystallization. The hydrochloride has a melting point of 278 to 280 ° C (from alcohol and a little water).
3. N- [1,1 -Diphenyl-1 -hydroxy-propyl-(2)]-norgränatan 3. N- [1,1-Diphenyl-1-hydroxy-propyl- (2)] - norgrenatan
a) Eine Lösung von Brompropiophenon, die durch langsames Zutropfen von 16 g Brom zu einer Lösung von 13,4 g Propiophenon in 30 ml Methylenchlorid bei 20 bis 25 0C unter Rühren erhalten worden ist, wird noch 1 Stunde weitergerührt und darauf bei 15 bis 20° C mit einer Aufschlämmung von 28,6 g Norgranatan (festes, wasserhaltiges Produkt) in 20 ml Wasser in kleinen Portionen nach und nach versetzt. Man rührt 6 Stunden bei Zimmertemperatur nach, schüttelt mit verdünnter Salzsäure aus und macht die saure, wäßrige Lösung mit 10 η-Natronlauge alkalisch. Die Base wird mit Äther aufgenommen, die Ätherlösung getrocknet, eingeengt und der Rückstand destilliert. Man erhält 10,3 g l-Phenyl-2-(N-norgranatanyl)-propanon-(l) vom Kp.0,6 165 bis 172° C; die Ausbeute beträgt 40%.a) A solution of bromopropiophenone, which has been obtained by slowly adding dropwise 16 g of bromine to a solution of 13.4 g of propiophenone in 30 ml of methylene chloride at 20 to 25 0 C with stirring, is stirred for a further 1 hour and then at 15 to 20 ° C with a slurry of 28.6 g of norgranatan (solid, water-containing product) in 20 ml of water in small portions gradually added. The mixture is stirred for 6 hours at room temperature, extracted with dilute hydrochloric acid and the acidic, aqueous solution is made alkaline with 10 η sodium hydroxide solution. The base is taken up with ether, the ether solution is dried and concentrated and the residue is distilled. 10.3 g of l-phenyl-2- (N-norgranatanyl) -propanon- (l) with a boiling point of 0.6 165 to 172 ° C are obtained; the yield is 40%.
b) Zu einer aus 4,1 g Magnesium und 26,5 g Brombenzol in 150 ml Äther hergestellten Phenylmagnesiumbromidlösung tropft man eine Lösung von 21,5 g l-Phenyl-2-(N-norgranatanyl)-propanon-(l) in 50 ml Äther langsam zu, wobei nötigenfalls gekühlt wird, um die Temperatur nicht über 300C ansteigen zu lassen. Anschließend erhitzt man 4 Stunden am Rückfluß und gibt schließlich etwa 20 ml gesättigte Ammoniumchloridlösung langsam zu. Das Reaktionsprodukt wird mit 3,51 Äther aufgenommen, die Ätherlösung getrocknet und bis auf etwa 100 ml eingeengt. Die ausgefallenen Kristalle werden abgesaugt und mit Äther nachgewaschen. Man erhält 18,2 , N-[1,1-Diphenyl-1-hydroxy-propyl-(2)]-norgranatan; die Ausbeute beträgt 64,8%. Die Substanz schmilzt nach dem Umkristallisieren aus Essigester bei 168 bis 169 0C. Hydrochlorid: F. 246°C (Zersetzung).b) A solution of 21.5 g of l-phenyl-2- (N-norgranatanyl) -propanone- (l) in 50 is added dropwise to a phenylmagnesium bromide solution prepared from 4.1 g of magnesium and 26.5 g of bromobenzene in 150 ml of ether ml of ether are slowly added, cooling if necessary so as not to allow the temperature to rise above 30 ° C. The mixture is then refluxed for 4 hours and finally about 20 ml of saturated ammonium chloride solution are slowly added. The reaction product is taken up with 3.51 ether, the ether solution is dried and concentrated to about 100 ml. The precipitated crystals are suctioned off and washed with ether. 18,2, N- [1,1-diphenyl-1-hydroxypropyl- (2)] - norgranatane is obtained; the yield is 64.8%. The substance melts after recrystallization from Essigester at 168-169 0 C. hydrochloride: mp 246 ° C (decomposition).
Claims (1)
P. K a r r e r, Lehrbuch der Organischen Chemie,Considered publications:
P. K arrer, Textbook of Organic Chemistry,
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1962B0065780 DE1162847B (en) | 1962-02-02 | 1962-02-02 | Process for the preparation of N-diphenylalkyl-norgranatane and -nortropane derivatives. |
| CH931866A CH420167A (en) | 1962-02-02 | 1963-01-31 | Process for the preparation of new N-diphenylalkyl-norgranatan- and -nortropane derivatives |
| CH118363A CH419141A (en) | 1962-02-02 | 1963-01-31 | Process for the preparation of new N-diphenylalkyl-norgranatan- and -nortropane derivatives |
| GB4015/63A GB961516A (en) | 1962-02-02 | 1963-01-31 | New n-diphenylalkyl-norgranatane derivatives |
| BE627904A BE627904A (en) | 1962-02-02 | 1963-02-01 | New derivatives of N-diphenylalkylnorgranatane and nortropane and process for preparing them |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1962B0065780 DE1162847B (en) | 1962-02-02 | 1962-02-02 | Process for the preparation of N-diphenylalkyl-norgranatane and -nortropane derivatives. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1162847B true DE1162847B (en) | 1964-02-13 |
Family
ID=6974904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1962B0065780 Pending DE1162847B (en) | 1962-02-02 | 1962-02-02 | Process for the preparation of N-diphenylalkyl-norgranatane and -nortropane derivatives. |
Country Status (4)
| Country | Link |
|---|---|
| BE (1) | BE627904A (en) |
| CH (2) | CH419141A (en) |
| DE (1) | DE1162847B (en) |
| GB (1) | GB961516A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1219943B (en) * | 1964-06-30 | 1966-06-30 | Boehringer & Soehne Gmbh | Process for the preparation of esters of N- (hydroxyalkyl) -nortropanes or -norgranatanes and their salts |
-
1962
- 1962-02-02 DE DE1962B0065780 patent/DE1162847B/en active Pending
-
1963
- 1963-01-31 CH CH118363A patent/CH419141A/en unknown
- 1963-01-31 GB GB4015/63A patent/GB961516A/en not_active Expired
- 1963-01-31 CH CH931866A patent/CH420167A/en unknown
- 1963-02-01 BE BE627904A patent/BE627904A/en unknown
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1219943B (en) * | 1964-06-30 | 1966-06-30 | Boehringer & Soehne Gmbh | Process for the preparation of esters of N- (hydroxyalkyl) -nortropanes or -norgranatanes and their salts |
Also Published As
| Publication number | Publication date |
|---|---|
| CH420167A (en) | 1966-09-15 |
| GB961516A (en) | 1964-06-24 |
| BE627904A (en) | 1963-08-01 |
| CH419141A (en) | 1966-08-31 |
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