CH544754A - N-ethyl-2-aminomethyl pyrrolidine prepn - by reacting tetrahydrofurylami-ne with HBr and ring-closure of cpd obtd with monoethylamine - Google Patents
N-ethyl-2-aminomethyl pyrrolidine prepn - by reacting tetrahydrofurylami-ne with HBr and ring-closure of cpd obtd with monoethylamineInfo
- Publication number
- CH544754A CH544754A CH1852772A CH1852772A CH544754A CH 544754 A CH544754 A CH 544754A CH 1852772 A CH1852772 A CH 1852772A CH 1852772 A CH1852772 A CH 1852772A CH 544754 A CH544754 A CH 544754A
- Authority
- CH
- Switzerland
- Prior art keywords
- ethyl
- aminomethyl pyrrolidine
- hours
- formula
- benzene
- Prior art date
Links
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 title claims abstract description 15
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 title claims description 15
- 238000006798 ring closing metathesis reaction Methods 0.000 title abstract 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 10
- YNOGYQAEJGADFJ-UHFFFAOYSA-N oxolan-2-ylmethanamine Chemical compound NCC1CCCO1 YNOGYQAEJGADFJ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 3
- -1 e.g. Substances 0.000 claims abstract description 3
- 239000000126 substance Substances 0.000 claims abstract description 3
- 238000000605 extraction Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 8
- PQAAKVCEMOJBLC-UHFFFAOYSA-N 5,5-dibromopentan-1-amine Chemical compound NCCCCC(Br)Br PQAAKVCEMOJBLC-UHFFFAOYSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 239000012071 phase Substances 0.000 claims description 6
- ITIBDHSKPVMGBC-UHFFFAOYSA-N 2,5-dibromopentan-1-amine;hydrobromide Chemical compound Br.NCC(Br)CCCBr ITIBDHSKPVMGBC-UHFFFAOYSA-N 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000004064 recycling Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- 239000012736 aqueous medium Substances 0.000 claims description 2
- 239000008346 aqueous phase Substances 0.000 claims description 2
- 230000001174 ascending effect Effects 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 238000004817 gas chromatography Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000002609 medium Substances 0.000 claims description 2
- ZNWIIPXBIAISRZ-UHFFFAOYSA-N n,n-dibromopentan-1-amine Chemical compound CCCCCN(Br)Br ZNWIIPXBIAISRZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 239000012429 reaction media Substances 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Title cpd. (I), useful as a synethesis inter. in chemical and pharmaceutical ind., is prepd. by (a) reacting HBr gas for 4-5 hrs. at 100 degrees C with tetrahydrofurfurylamine, to effect ring opening, and (b) reacting Br-(CH2)3-CHBr-CH2-NH2 obtd. with EtNH2, at ambient temp. for 48 hrs., with ring-closure to (I) which is then (c) sepd. from reaction mixt. by extn. with benzene or with a chlorinated solvent, e.g., CHCl3 or CH2Cl2, and purified pref. by distn. at 15 mm Hg.
Description
La présente invention a pour objet un procédé de préparation de la N-éthyl 2 aminométhyl pyrrolidine.
Ce produit est très sollicité en tant qu'intermédiaire de synthèse dans l'industrie chimique et pharmaceutique et c'est la raison pour laquelle un procédé simple et rapide de sa fabrication présente un grand intérêt.
Le procédé selon l'invention pour la préparation de la N-éthyl 2 aminométhyl pyrrolidine de formule:
EMI1.1
est caractérisé par les étapes suivantes:
a. on fait réagir l'acide bromhydrique gaz, pendant 4 à 5 heures et à une température en dessous de 100"C, avec la tétrahydrofurfurylamine de formule:
EMI1.2
pour obtenir, par ouverture du cycle, la 2,5 dibromopentylamine de formule:
EMI1.3
b. on fait réagir la 2,5 dibromopentylamine obtenue, à la température ambiante pendant 48 heures, avec la monoéthylamine pour former par recyclisation la N-éthyl 2 aminométhyl pyrrolidine, et
c. on sépare et purifie celleci du milieu réactionnel.
La séparation se fait de préférence par extraction au benzène ou à l'aide d'un solvant chloré comme par exemple le chloroform ou le chlorure de méthylène. La N-éthyl 2 aminométhyl pyrrolidine est ensuite purifiée, de préférence par distillation sous une pression de 15 mmHg, de la phase d'extraction qui la contient.
Le procédé selon l'invention peut être représenté par le schéma de réaction indiqué ci-dessous:
EMI1.4
L'invention sera illustrée par l'exemple qui suit:
Exemple
Dans un ballon d'un litre à 3 tubulures muni d'un thermomè tre, d'un agitateur mécanique, d'un réfrigérant ascendant et d'un tube plongeant pour introduction de gaz, on dissout:
tétrahydrofurfurylamine: 101 g(l mol.)dans:
acide acétique: 100 g
On introduit dans cette solution:
- acide bromhydrique gaz: 267 g (3,3 mol.)
Une fois l'introduction de l'acide bromhydrique terminée, on chauffe progressivement pendant 4 à 5 heures et à une température jusqu'à 100"C et ensuite on laisse refroidir à la température ambiante.
On essore le précipité cristallin de bromhydrate de 2,5 dibromo-pentylamine et le lave avec de l'éther.
Dans un récipient de 10 litres, avec fermeture hermétique. on introduit:
bromhydrate de 2,5 dibromo-pentylamine humide obtenu puis une
- solution benzénique à 10% de monoéthylamine: 4 1.
On ferme le récipient et le garde à la température ambiante au repos pendant 48 heures en le secouant de temps en temps. On ajoute:
- lessive de soude à 30%: 400 ml et on agite bien le milieu. Ensuite on introduit environ I kilo de soude en paillettes. On décante la couche benzénique et effectue encore deux à trois extractions en benzène sur la phase aqueuse.
On réunit les phases benzéniques et distille avec une colonne de vigreux ou une colonne à plateaux. On recueille la fraction qui passe à 65 -70 sous 15 mmHg et obtient 77 grammes de N-éthyl 2 aminométhyl pyrrolidine pure, soit un rendement d'environ 60%. Les extractions peuvent être effectuées aussi avec un solvant chloré.
Propriétés analytiques de la N-étliyl 2 aniiton2étkti pyrroliclitie
- liquide mobile incolore ou légèrement jaune - densité à 20 C = 0,896 à 0.899
- indice de réfraction à 20 C = 1,467 à I 470
- P.E. sous 760 mm = 175-178
dosage en milieu non aqueux: 98-100%
- pureté par chromatographie en phase gazeuse = supé
rieure à 98%.
REVENDICATION
Procédé de préparation de la N-éthyl 2 aminométhyl pyrrolidine de formule:
EMI1.5
caractérisé en ce qu'il comprend les étapes suivantes: a. on fait réagir l'acide bromhydrique gazeux. pendant 4 il 5 heures et à une température en dessous de 100 C. avec la tétrahydrofurfurylamine de formule:
EMI1.6
pour obtenir, par ouverture du cycle, la 2.5 dibromo-pentylamine de formule:
EMI1.7
b. on fait réagir la 2.5 dibromo-pentylamine obtenue. à la température ambiante pendant 48 heures, avec la monoéthylamine pour former par recyclisation la N-éthyl 2 aminométhyl pyrrolidine que
c. I'on sépare et purifie du mélange réactionnel.
SOUS-REVENDICATIONS
1. Procédé selon la revendication. caractérisé en ce que la séparation est faite par extraction avec un solvant chlore choisi parmi le chloroforme et le chlorure de méthylène.
2. Procédé selon la revendication et la sous-revendication 1.
caractérisé en ce que l'on purifie la N-éthyl 2 aminométhyl pyrrolidine par distillation, sous 15 mmHg, de la phase d'extraction.
**ATTENTION** fin du champ DESC peut contenir debut de CLMS **.
The present invention relates to a process for the preparation of N-ethyl 2 aminomethyl pyrrolidine.
This product is in great demand as a synthetic intermediate in the chemical and pharmaceutical industry and this is the reason why a simple and rapid process for its manufacture is of great interest.
The process according to the invention for the preparation of N-ethyl 2 aminomethyl pyrrolidine of formula:
EMI1.1
is characterized by the following steps:
at. the hydrobromic acid gas is reacted for 4 to 5 hours and at a temperature below 100 ° C., with the tetrahydrofurfurylamine of formula:
EMI1.2
to obtain, by opening the ring, 2.5 dibromopentylamine of formula:
EMI1.3
b. the 2.5 dibromopentylamine obtained is reacted at room temperature for 48 hours with monoethylamine to form, by recycling, N-ethyl 2 aminomethyl pyrrolidine, and
vs. it is separated and purified from the reaction medium.
The separation is preferably carried out by extraction with benzene or with the aid of a chlorinated solvent such as, for example, chloroform or methylene chloride. The N-ethyl 2 aminomethyl pyrrolidine is then purified, preferably by distillation under a pressure of 15 mmHg, from the extraction phase which contains it.
The process according to the invention can be represented by the reaction scheme indicated below:
EMI1.4
The invention will be illustrated by the following example:
Example
In a one-liter 3-neck flask fitted with a thermometer, a mechanical stirrer, an ascending condenser and a dip tube for introducing gas, the following are dissolved:
tetrahydrofurfurylamine: 101 g (l mol.) in:
acetic acid: 100 g
We introduce into this solution:
- gas hydrobromic acid: 267 g (3.3 mol.)
Once the introduction of hydrobromic acid is completed, it is gradually heated for 4 to 5 hours and at a temperature up to 100 ° C. and then allowed to cool to room temperature.
The crystalline precipitate of 2,5 dibromopentylamine hydrobromide is filtered off with suction and washed with ether.
In a 10 liter container, with airtight closure. we introduce:
wet 2,5 dibromopentylamine hydrobromide obtained then a
- 10% benzene solution of monoethylamine: 4 1.
The container is closed and kept at room temperature standing for 48 hours, shaking it occasionally. We add:
- 30% sodium hydroxide solution: 400 ml and the medium is stirred well. Then we introduce about 1 kilo of soda flakes. The benzene layer is decanted and a further two to three benzene extractions are carried out on the aqueous phase.
The benzene phases are combined and distilled with a vigreux column or a plate column. The fraction which passes to 65 -70 under 15 mmHg is collected and 77 grams of pure N-ethyl 2-aminomethyl pyrrolidine are obtained, ie a yield of approximately 60%. Extractions can also be carried out with a chlorinated solvent.
Analytical properties of N-etliyl 2 aniiton2étkti pyrroliclitie
- colorless or slightly yellow mobile liquid - density at 20 C = 0.896 to 0.899
- refractive index at 20 C = 1.467 at I 470
- P.E. under 760 mm = 175-178
dosage in non-aqueous medium: 98-100%
- purity by gas chromatography = superior
98% higher.
CLAIM
Process for preparing 2-N-ethyl aminomethyl pyrrolidine of formula:
EMI1.5
characterized in that it comprises the following steps: a. gaseous hydrobromic acid is reacted. for 4 to 5 hours and at a temperature below 100 C. with tetrahydrofurfurylamine of formula:
EMI1.6
to obtain, by opening the ring, 2.5 dibromo-pentylamine of formula:
EMI1.7
b. the 2.5 dibromopentylamine obtained is reacted. at room temperature for 48 hours, with monoethylamine to form by recycling the N-ethyl 2 aminomethyl pyrrolidine which
vs. It is separated and purified from the reaction mixture.
SUB-CLAIMS
1. Method according to claim. characterized in that the separation is carried out by extraction with a chlorine solvent chosen from chloroform and methylene chloride.
2. Method according to claim and sub-claim 1.
characterized in that the N-ethyl 2 aminomethyl pyrrolidine is purified by distillation, under 15 mmHg, of the extraction phase.
** ATTENTION ** end of DESC field can contain start of CLMS **.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1852772A CH544754A (en) | 1972-12-21 | 1972-12-21 | N-ethyl-2-aminomethyl pyrrolidine prepn - by reacting tetrahydrofurylami-ne with HBr and ring-closure of cpd obtd with monoethylamine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1852772A CH544754A (en) | 1972-12-21 | 1972-12-21 | N-ethyl-2-aminomethyl pyrrolidine prepn - by reacting tetrahydrofurylami-ne with HBr and ring-closure of cpd obtd with monoethylamine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH544754A true CH544754A (en) | 1974-01-15 |
Family
ID=4433605
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1852772A CH544754A (en) | 1972-12-21 | 1972-12-21 | N-ethyl-2-aminomethyl pyrrolidine prepn - by reacting tetrahydrofurylami-ne with HBr and ring-closure of cpd obtd with monoethylamine |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH544754A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5277057A (en) * | 1975-12-19 | 1977-06-29 | Sachim Sa | Production of nnalkenyll22 aminomethylpyrolidines* |
| JPS5363375A (en) * | 1976-11-15 | 1978-06-06 | Teikoku Hormone Mfg Co Ltd | Preparation of substd. benzoic acid amide derivatives |
-
1972
- 1972-12-21 CH CH1852772A patent/CH544754A/en not_active IP Right Cessation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5277057A (en) * | 1975-12-19 | 1977-06-29 | Sachim Sa | Production of nnalkenyll22 aminomethylpyrolidines* |
| JPS5363375A (en) * | 1976-11-15 | 1978-06-06 | Teikoku Hormone Mfg Co Ltd | Preparation of substd. benzoic acid amide derivatives |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |