BE818471A - PROCESS FOR PREPARING 1-ARALKYL-4-AMINO-METHYLPIPERIDINE-4-OLS - Google Patents
PROCESS FOR PREPARING 1-ARALKYL-4-AMINO-METHYLPIPERIDINE-4-OLSInfo
- Publication number
- BE818471A BE818471A BE147274A BE147274A BE818471A BE 818471 A BE818471 A BE 818471A BE 147274 A BE147274 A BE 147274A BE 147274 A BE147274 A BE 147274A BE 818471 A BE818471 A BE 818471A
- Authority
- BE
- Belgium
- Prior art keywords
- emi
- aralkyl
- amino
- preparing
- ols
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/40—Oxygen atoms
- C07D211/44—Oxygen atoms attached in position 4
- C07D211/48—Oxygen atoms attached in position 4 having an acyclic carbon atom attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Hydrogenated Pyridines (AREA)
Description
Procédé pour préparer des 1-aralkyl-4-amino-
<EMI ID=1.1>
<EMI ID=2.1>
de sodium, puis par traitement avec du cyanure de potassium dans de l'éther éthylique et on isole alors les cyanohydrines qu'on ré-duit au moyen d'hydrure de lithiumaluminium dans du tétrahydro-
<EMI ID=3.1> <EMI ID=4.1>
Durant la dernière réaction une hydrogénolyse partielle
a lieu avec formation de 1-aralkylpipéridine-4-ol à raison de
26%, sur base de la quantité de cyanohydrine de 1-aralkylpipéridone.
Suivant la présente invention, on prépara les mêmes 1-
<EMI ID=5.1>
<EMI ID=6.1>
où R représente un radical benzyle ou phénéthyle,à partir des
<EMI ID=7.1>
<EMI ID=8.1>
où R représente un radical benzyle ou phénétyle,qu'on convertit
en présence d'éthylate de sodium,par réaction avec du nitrométhane dans de l'éthanol absolu et à la température ambiante,en
<EMI ID=9.1>
<EMI ID=10.1>
où R représente un radical benzyle ou phénétyle.
Ces derniers composés, par réduction avec du zinc dans
un acide minéral,comme l'acide chlorhydrique ou l'acide sulfurique,
<EMI ID=11.1>
rale :
<EMI ID=12.1>
<EMI ID=13.1>
Cette réduction non seulement ne conduit à aucune hydrogénolys�, mais permet d'obtenir le produit recherché dans un rendement quasi tuantitatif.
Le procédé de l'invention permet également la conversion des composés de formule IV en les ominoalcools correspondants de formule générale I.
EXEMPLE 1.-
A une solution d'éthylate de sodium,obtenue par dissolution de 6,2 g de sodium dans 130 ml d'éthanol absolu assez rapidement
<EMI ID=14.1>
4-one dans 20 g de nitrométhane et 50 ml d'éthanol absolu pour obtenir un précipité abondant qu'on agite vivement pendant 2 heures, puis qu'on isole par filtration sous vide. On dissout le produit dans 300 ml d'eau, on acidifie modérément la solution sous agitation au moyen de 15 ml d'acide acétique, puis on filtre le mélange
<EMI ID=15.1>
Un échantillon recristallisé dans l'acétate d'éthyle fond à 119-120[deg.]C.
<EMI ID=16.1>
solution dans 1 litre d'éthanol, on ajoute 90 g de zinc en granules, on agite le mélange et on y ajoute 600 ml d'acide chlorhydrique à
<EMI ID=17.1>
tation pendant 6 heures, puis on isole par filtration le métal inchangé et on concentre le filtrat sous vide jusqu'à la consistance d'un sirop,après quoi on ajoute 300 ml d'alcool absolu, on agite le mélange et on isole par filtration le produit blanc qui se sépare et qu'on sèche.
<EMI ID=18.1>
Calculé Zn 15,14; N 6,49; Cl 35,18%
Trouvé Zn 15,02; N 6,31; Cl 35,30�.
EXEMPLE -;.-
A 100 g du produit d'addition obtenu à l'exemple 2, on
<EMI ID=19.1>
pendant quelques minutes, on le dilue jusqu'à 1 litre au moyen d'eau et on extrait le mélange avec 3 fractions de 300 ml de chloroforme. On sèche les extraits chloroformiques combinés sur du sulfate de sodium, puis on les porte à siccité sous vide,
<EMI ID=20.1>
chlorhydrate fond à 243-244[deg.]C.
REVENDICATIONS
<EMI ID=21.1>
<EMI ID=22.1>
où R représente un radical benzyle ou phénétyle, caractérisé en
ce qu'on réduit les 1-aralkyl-4-nitrométhylpipéridine-4-als correspondants de formule générale :
<EMI ID=23.1>
où R a la signification indiquée ci-dessus, eux-mêmes obtenus par
<EMI ID=24.1>
méthane.
<EMI ID=25.1>
Process for preparing 1-aralkyl-4-amino-
<EMI ID = 1.1>
<EMI ID = 2.1>
sodium, then by treatment with potassium cyanide in ethyl ether and the cyanohydrins are then isolated which are reduced by means of lithium aluminum hydride in tetrahydro-
<EMI ID = 3.1> <EMI ID = 4.1>
During the last reaction partial hydrogenolysis
takes place with the formation of 1-aralkylpiperidin-4-ol at a rate of
26%, based on the amount of cyanohydrin of 1-aralkylpiperidone.
According to the present invention, the same 1-
<EMI ID = 5.1>
<EMI ID = 6.1>
where R represents a benzyl or phenethyl radical, from
<EMI ID = 7.1>
<EMI ID = 8.1>
where R represents a benzyl or phenethyl radical, which is converted
in the presence of sodium ethoxide, by reaction with nitromethane in absolute ethanol and at room temperature, in
<EMI ID = 9.1>
<EMI ID = 10.1>
where R represents a benzyl or phenethyl radical.
These latter compounds, by reduction with zinc in
a mineral acid, such as hydrochloric acid or sulfuric acid,
<EMI ID = 11.1>
rale:
<EMI ID = 12.1>
<EMI ID = 13.1>
This reduction not only does not lead to any hydrogenolys, but makes it possible to obtain the desired product in an almost killing yield.
The process of the invention also allows the conversion of the compounds of formula IV into the corresponding ominoalcohols of general formula I.
EXAMPLE 1.-
Has a solution of sodium ethoxide, obtained by dissolving 6.2 g of sodium in 130 ml of absolute ethanol fairly quickly
<EMI ID = 14.1>
4-one in 20 g of nitromethane and 50 ml of absolute ethanol to obtain an abundant precipitate which is stirred vigorously for 2 hours and then isolated by filtration under vacuum. The product is dissolved in 300 ml of water, the solution is moderately acidified with stirring using 15 ml of acetic acid, then the mixture is filtered.
<EMI ID = 15.1>
A sample recrystallized from ethyl acetate melts at 119-120 [deg.] C.
<EMI ID = 16.1>
solution in 1 liter of ethanol, 90 g of granulated zinc are added, the mixture is stirred and 600 ml of hydrochloric acid are added to
<EMI ID = 17.1>
tation for 6 hours, then the unchanged metal is isolated by filtration and the filtrate is concentrated in vacuo to the consistency of a syrup, after which 300 ml of absolute alcohol is added, the mixture is stirred and isolated by filtration. the white product which separates and is dried.
<EMI ID = 18.1>
Calculated Zn 15.14; N 6.49; Cl 35.18%
Found Zn 15.02; N 6.31; Cl 35.30 �.
EXAMPLE -; .-
To 100 g of the adduct obtained in Example 2, one
<EMI ID = 19.1>
for a few minutes it is diluted to 1 liter with water and the mixture is extracted with 3 portions of 300 ml of chloroform. The combined chloroform extracts are dried over sodium sulphate, then brought to dryness in vacuo,
<EMI ID = 20.1>
hydrochloride melts at 243-244 [deg.] C.
CLAIMS
<EMI ID = 21.1>
<EMI ID = 22.1>
where R represents a benzyl or phenethyl radical, characterized in
which reduces the corresponding 1-aralkyl-4-nitromethylpiperidine-4-als of general formula:
<EMI ID = 23.1>
where R has the meaning indicated above, themselves obtained by
<EMI ID = 24.1>
methane.
<EMI ID = 25.1>
Claims (1)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT3006973A IT1046052B (en) | 1973-10-12 | 1973-10-12 | 1-Aralkyl-4-aminomethyl-piperidin-4-ols prepn - by redn of corresp. 4-nitromethyl-piperidine-4-ols |
Publications (1)
Publication Number | Publication Date |
---|---|
BE818471A true BE818471A (en) | 1974-12-02 |
Family
ID=11228970
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BE147274A BE818471A (en) | 1973-10-12 | 1974-08-02 | PROCESS FOR PREPARING 1-ARALKYL-4-AMINO-METHYLPIPERIDINE-4-OLS |
Country Status (2)
Country | Link |
---|---|
BE (1) | BE818471A (en) |
IT (1) | IT1046052B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2498599A1 (en) * | 1981-01-28 | 1982-07-30 | Sandoz Sa | NOVEL 4-AMINOMETHYLPOLYALKYLPIPERIDINES AS STABILIZERS OF POLYMERS AND THEIR PREPARATION |
WO1999002494A1 (en) * | 1997-07-11 | 1999-01-21 | Janssen Pharmaceutica N.V. | Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
CN102766147A (en) * | 2012-08-03 | 2012-11-07 | 无锡药兴医药科技有限公司 | Method for preparing fenspiride and halogen acid salt thereof |
-
1973
- 1973-10-12 IT IT3006973A patent/IT1046052B/en active
-
1974
- 1974-08-02 BE BE147274A patent/BE818471A/en unknown
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2498599A1 (en) * | 1981-01-28 | 1982-07-30 | Sandoz Sa | NOVEL 4-AMINOMETHYLPOLYALKYLPIPERIDINES AS STABILIZERS OF POLYMERS AND THEIR PREPARATION |
WO1999002494A1 (en) * | 1997-07-11 | 1999-01-21 | Janssen Pharmaceutica N.V. | Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
US6452013B1 (en) | 1997-07-11 | 2002-09-17 | Janssen Pharmaceutica N.V. | Gastrokinetic monocyclic benzamides of 3- or 4-substituted 4-(aminomethyl)-piperidine derivatives |
US6750349B2 (en) | 1997-07-11 | 2004-06-15 | Janssen Pharmaceutics, N.V. | Gastrokinetic monocyclic benzamides of 3-or 4-substituted 4-(aminoethyl)-piperidine derivatives |
CN102766147A (en) * | 2012-08-03 | 2012-11-07 | 无锡药兴医药科技有限公司 | Method for preparing fenspiride and halogen acid salt thereof |
Also Published As
Publication number | Publication date |
---|---|
IT1046052B (en) | 1980-06-30 |
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