EP1699770A1 - Procede de synthese de derives de cycloalkyl-hydrazines exocycliques et de derives d'heterocycloalkyl-hydrazines exocycliques - Google Patents
Procede de synthese de derives de cycloalkyl-hydrazines exocycliques et de derives d'heterocycloalkyl-hydrazines exocycliquesInfo
- Publication number
- EP1699770A1 EP1699770A1 EP04816423A EP04816423A EP1699770A1 EP 1699770 A1 EP1699770 A1 EP 1699770A1 EP 04816423 A EP04816423 A EP 04816423A EP 04816423 A EP04816423 A EP 04816423A EP 1699770 A1 EP1699770 A1 EP 1699770A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- hydrazine
- solution
- exocyclic
- heterocycloalkyl
- cycloalkyl
- 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.)
- Withdrawn
Links
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
- C07D295/22—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 hetero atoms directly attached to ring nitrogen atoms
- C07D295/28—Nitrogen atoms
- C07D295/30—Nitrogen atoms non-acylated
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
Definitions
- the present invention relates to a new process for the synthesis of exocyclic cycloalkyl hydrazine derivatives and exocyclic heterocycloalkyl hydrazine derivatives.
- Cycloalkyl hydrazine derivatives and exocyclic heterocycloalkyl hydrazines, in particular N-aminopiperidine, are very frequently used as intermediates in the manufacture of medicaments.
- a second method consists of a nitrosation of piperidine followed by a chemical hydrogenation (LiAlH 4 ) or catalytic (Zn / AcOH) of the nitrose derivative (1-nitrosopiperidine) (Allen & Hanburys Ltd. (1965), 74, 3693-4 ).
- the nitrosed compound must be purified by distillation.
- This method leads to fairly good yields (75%).
- the product resulting from the first stage must be handled with great care because of its toxicity (highly carcinogenic compound), which poses industrial problems of exploitation.
- the use of LiAlH 4 imposes the absence of traces of water, sealed reactors and anhydrous solvents (diethyl ether), which has the effect of increasing the risks of ignition of the reaction mixture.
- Patent EP 0277267 describes a process for the continuous synthesis of N-amino aza-3 bicyclo [3,3,0] octane, characterized in that a solution of ammonium hydroxide and chloride is reacted ammonium with an aqueous solution of sodium hypochlorite at a temperature between -15 ° C and -7 ° C in an alkaline medium, and then reacting the monochloramine thus formed with aza-3 bicyclo [3 , 3.0] octane, in a two-phase medium in a suitable reactor fitted with a coaxial stirrer with fins, at a temperature between 30 ° C and 90 ° C and in an alkaline medium, then separated from the rammoniac reaction medium and then the aza-3 bicyclo [3,3,0] octane which has not reacted by distillation to recycle it, and then a concentrated solution of N-amino aza-3 bicyclo [3 is isolated by demixing) 3.0]
- reaction solution After formation of N-amino aza-3 bicyclo [3,3,0] octane and cooling, the reaction solution undergoes degassing to remove ammonia and 3-amino bicyclo [3,3,0] octane which does not unreacted is separated from the reaction medium by simple distillation under atmospheric pressure and at a temperature of about 90 to 100 ° C. Under these conditions, the amine is obtained in the form of an aqueous solution concentrated to 30% in aza-3 bicyclo [3,3,0] octane. This solution is recycled.
- the inventors have now discovered a new process for the synthesis of exocyclic cycloalkyl hydrazine derivatives and exocyclic heterocycloalkyl hydrazine derivatives, in particular N-aminopiperidine.
- This process implemented in continuous is partly based on a transposition of the Raschig process, and it consists in preparing the monochloramine by action of sodium hypochlorite on ammonia at low temperature, and then in making the monochloramine thus produced act on a heterocyclic amine in medium homogeneous or, depending on the temperature, in a heterogeneous medium, then to extract the hydrazine formed.
- the starting amine is recycled, then if necessary reinjected directly onto the monochloramine without any additional treatment.
- exocyclic cycloalkyl-hydrazine derivative (s) and the exocyclic heterocycloalkyl-hydrazine derivative (s) may be designated by the term "hydrazine (s)".
- the expression “exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine” should read “exocyclic cycloalkyl-hydrazine derivative or exocyclic heterocycloalkyl-hydrazine derivative”.
- the hetero cyclic amine (s) may be designated by the term "amine (s)”.
- the present invention thus relates to a process for the synthesis of exocyclic cycloalkylhydrazine derivatives and exocyclic heterocycloalkyl-hydrazine derivatives, characterized in that it comprises the following successive steps: a) synthesizing the cycloalkyl-hydrazine derivative or heterocycloalkyl - exocyclic hydrazine in a suitable reactor by reacting in an alkaline medium and at a temperature between 30 and 60 ° C a monochloramine with a heterocyclic amine; then b) demixing the solution obtained following step a) into an organic phase and an aqueous phase by adding anhydrous sodium hydroxide under cooling so that the temperature does not exceed the boiling point of the compounds; and c) if necessary, isolating, by distillation of the organic phase thus obtained, the exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine.
- exocyclic cycloalkyl-hydrazine or exocyclic heterocycloalkyl-hydrazine derivative is advantageously of formula (I) in which one of the carbon atoms of the ring is optionally replaced by a heteroatom chosen from a nitrogen or oxygen atom, RI and R2, identical or different, represent a hydrogen atom or a C ⁇ -C 6 alkyl radical or RI and R2 together form a C 3 -C 8 cycloalkyl and n is 1 to 3.
- the exocyclic cycloalkyl-hydrazine or heterocycloalkyl-hydrazine derivative is even more advantageously chosen from the group consisting of N-aminopiperidine, N-aminomorpholine, N-amino-2,6-dimethyl-piperidine, N-aminopyrrolidine , N-aminoazepine, N-amino-4-methyl-piperazine.
- the reactor of step a) is advantageously placed under an inert atmosphere, in particular under an argon or nitrogen sweep.
- Said suitable reactor of step a) is advantageously a stirred tabular reactor.
- the tubular reactor makes it possible to avoid contact between the nascent hydrazine and the monochloramine and thus it makes it possible to avoid an oxidation-reduction reaction between these two reactants.
- the reaction front moves along the tube and the hydrazine is no longer in contact with the monochloramine injected at the base of the reactor.
- the concentration of hydroxyl ions in the reaction medium of step a) is between 0.3 and 0.8 mol.l "1.
- the ratio of the molar concentrations of the amine heterocyclic on the monochloramine must advantageously be greater than or equal to 4 and less than or equal to 10.
- the reaction time is variable and depends on the temperature at which the reaction is carried out and on the ratio of the concentrations of the reactants. in the case of the synthesis of N-aminopiperidine and in the range of concentration ratios given, the reaction time is of the order of 20 seconds to 2 minutes at 25 ° C. and of the order of 4 seconds to 30 seconds at 60 ° C.
- the monochloramine is made alkaline before step a) in a mixer by adding a solution of a strong base such as sodium hydroxide so that the mass content of hydroxide sodium is between 2 and 6%.
- Said mixer is advantageously maintained at a temperature between -10 and 5 ° C.
- the reaction of monochloramine with the heterocyclic amine is thus advantageously carried out in the presence of an aqueous solution of sodium hydroxide when hot.
- the concentration of sodium hydroxide in the reaction medium is approximately 0.3 mol.L "1.
- the sodium hydroxide concentration must not be too high otherwise the reaction mixture risks demixing by salting out.
- a reactor of the agitated piston reactor type would then have to be used During the hydrazine synthesis reaction, hydrochloric acid is also formed, but any local protonation of the amine during mixing must be avoided in order to avoid the formation of a substituted chloramine.
- piperidine protonated by hydrochloric acid can react with monochloramine to form 1-chloropiperidine, which can then react with hydroxyl ions to form the 2,3,4,5-tetrahydropyridine, which then risks trimerizing.
- the alkalinization of monochloramine that is to say the addition of a strong base such as sodium hydroxide, thus makes it possible to neutralize the acid formed.
- the amount of strong base added must be sufficient to neutralize all the acid formed.
- the rate of formation of hydrazine increases with the alkalinity of the medium, which is not the case for the rate of degradation reactions, such as for example the oxidation of incipient hydrazine by chloramine .
- the amount of anhydrous sodium hydroxide added is such that the mass content of sodium hydroxide is between 10 and 35%, preferably approximately equal to 30%.
- the medium demixes into two phases, one of which concentrates the exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine formed in the light phase (organic phase).
- This sodium hydroxide treatment makes it possible, by demixing, to remove the water present in the reaction medium and to extract the salts and, where appropriate, the ammonia in the lower phase (aqueous phase).
- the temperature of the demixing medium of step b) must not exceed 80 ° C.
- the heterocyclic amine is introduced, in step a), in the form of an anhydrous heterocyclic amine.
- the monochloramine, advantageously alkalized, and the anhydrous heterocyclic amine are advantageously introduced simultaneously into the reactor.
- the addition rates of the heterocyclic amine and of the monochloramine are such that the ratio of the molar concentrations of the anhydrous heterocyclic amine to the monochloramine is advantageously between 4 and 10, the limits being able to be included.
- Part of the synthesis reaction of the cycloalkyl-hydrazine derivative and exocyclic heterocycloalkyl-hydrazine can be carried out in a heterogeneous medium.
- step b makes it possible to demix the medium into two phases, one of which, the upper phase or the organic phase concentrates almost all of the organics, namely the exocyclic cycloalkyl-hydrazine or heterocycloalkyl-hydrazine derivative and the heterocyclic amine.
- Step c) then advantageously comprises the following successive steps: i) isolating the heterocyclic amine which has not reacted and a concentrated solution of exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine by distillation of the organic phase obtained following step b); then ii) if necessary, rectify by distillation under reduced pressure said concentrated solution of the derivative of cycloalkyl-hydrazine and of exocyclic heterocycloalkyl-hydrazine.
- step i) the distillation is advantageously carried out in a single distillation column under atmospheric or reduced pressure, depending on the boiling temperature of the starting amine.
- a concentrated heterocyclic amine solution or, where appropriate, a heterocyclic water-amine azeotropic solution until the water is used up is collected at the top of the column, followed by the anhydrous heterocyclic amine.
- the anhydrous heterocyclic amine thus recovered can be reinjected directly into the reactor of step a) where the synthesis of hydrazine takes place.
- the heterocyclic amine obtained in the form of a concentrated solution or an azeotropic solution with water can be recovered, then optionally reinjected after an appropriate treatment.
- step i) rectification under reduced pressure, advantageously around 115 mm of Hg, of the product obtained at the bottom of the column in step i) makes it possible to collect the exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine with a higher titer at 99%, advantageously greater than 99.9%.
- Said exocyclic cycloalkyl-hydrazine or heterocycloalkyl-hydrazine derivative must then be stored under an inert atmosphere, such as under argon for example, so as to avoid any oxidation reaction with oxygen.
- This variant of the invention is particularly advantageous in the context of a batch preparation of the exocyclic cycloalkyl-hydrazine derivative or exocyclic heterocycloalkyl-hydrazine derivative.
- the heterocyclic amine is introduced, in step a), in the form of a concentrated aqueous solution of heterocyclic amine or of an azeotropic water-heterocyclic amine solution.
- Step a) is then carried out in a homogeneous or heterogeneous medium (in the case of a very heavy amine).
- the concentrated aqueous solution of heterocyclic amine may be in the form of a heterocyclic water-amine azeotrope.
- the monochloramine, advantageously alkalized, and the heterocyclic amine solution are advantageously introduced simultaneously into the reactor.
- the addition rates of the concentrated aqueous solution of heterocyclic amine, or of the azeotropic water-heterocyclic amine solution, and of the monochloramine are such that the ratio of the molar concentrations of the heterocyclic amine solution to the monochloramine is advantageously understood. between 4 and 10, the terminals may be included.
- the reaction mixture can optionally undergo one or more degassing step (s) to remove the ammonia contained in said mixture.
- the method comprises the following steps: i ') eliminating the ammonia present in the solution obtained following step a ) by stripping; then ii ') isolating a solution comprising the exocyclic hetero-cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine formed and a concentrated solution of unreacted heterocyclic amine, or if necessary a heterocyclic azeotropic water-amine solution which n 'has not reacted, by distillation of the solution obtained following step i') under atmospheric or reduced pressure at a temperature between 50 and 180 ° C; and iii ') reinjecting into the reactor of step a) said concentrated or azeotropic aqueous solution of heterocyclic amine obtained following step ii').
- the expression “stripping” is understood to mean the elimination of a very volatile product, in this case ammonia, by
- reaction solution containing hydrazine, recovered in step ii '), is then treated by adding a strong base, such as sodium hydroxide (step b)).
- a strong base such as sodium hydroxide
- This operation allows the separation of the exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine in an organic phase, having a titer between 70 and 90% hydrazine, depending on the organic character of the hydrazine molecule.
- the concentrated solution of hydrazine thus obtained can be used directly or distilled under reduced pressure (step c)).
- the amine is recycled during the distillation step ii '), without entraining the hydrazine and at a temperature below the boiling point of the amine, which avoids its thermo-degradation.
- the amine Given the absence of traces of hydrazine in the aqueous solution containing the heterocyclic amine, optionally in the form of an azeotrope, it can be injected, without additional treatment, directly at the stage reactor a), where hydrazine is formed.
- This variant of the invention is particularly advantageous in the context of a continuous preparation of the exocyclic cycloalkyl-hydrazine derivative or exocyclic heterocycloalkyl-hydrazine derivative.
- the process according to the present invention therefore allows not only the synthesis of the cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine exocyclic continuously, without the formation of any toxic intermediate, but it also allows the obtaining of said hydrazine with little cost Student.
- the classic Raschig synthesis generally requires a large excess of amine, which constitutes a considerable drawback when the amines used as raw material for the preparation of the corresponding hydrazines have a very high cost.
- the process of the present invention thanks to the recovery and recycling of a concentrated solution of heterocyclic amine, optionally in the form of an azeotrope, makes it possible to obtain the exocyclic cycloalkyl-hydrazine derivative or heterocycloalkyl-hydrazine corresponding with a very low cost compared to other known methods.
- the isolation of the amine in the form of an aqueous solution, optionally azeotropic, at relatively low temperature also constitutes another originality as well as a considerable economic advantage of the process according to the invention.
- the monochloramine introduced in step a) is advantageously prepared according to a process comprising the following successive steps: ci) preparing an aqueous solution of sodium hypochlorite having a chlorometric degree of between 36 and 100 ° optionally by dilution of a solution d hypochlorite having a chlorometric degree of between 100 and 120 °; then ⁇ ) reacting a solution of ammonium hydroxide and ammonium chloride with the aqueous solution of sodium hypochlorite obtained following step d), in a weakly alkaline medium, at a temperature between -15 and -7 ° C, to form said monochloramine.
- weakly alkaline medium is understood to mean a medium whose pH value is approximately 10 ⁇ 1.
- the molar ratio of ammonium hydroxide and ammonium chloride / aqueous solution of sodium hypochlorite is advantageously between 2.5 and 3, the limits being included.
- the molar ratio of chloride ammom 'um / ammonium hydroxide is advantageously between 0.1 and 1.75, the limits included, more preferably it is about 0.65.
- step ⁇ In the case where the chlorinated reagent used in step ⁇ ) is obtained by dilution of a high titer hypochlorite solution at 100-120 ° chlorometric, this dilution has the advantage of reducing the content of sodium chloride. This environmentally friendly treatment allows cooling of the bleach solution, without risk of crystallization down to -15 ° C.
- Example 1 gives, without limitation, a detailed description of the implementation of the method of the invention, the method of which the block diagram is shown in FIG. 1.
- CD1 distillation column n ° 1
- CD2 distillation column n ° 2
- Example 2 gives, without implied limitation, a detailed description of the implementation of the method of the invention, the method of which the principle diagram is represented in FIG. 2.
- N-amino-piperidine 3' Water solution + NH 3 + NaCl + NaOH
- EXAMPLE 1 Preparation of the N-amino piperidine continuously
- the monochloramine solution obtained above (2 liters) is made alkaline by continuous introduction of a concentrated solution of sodium hydroxide (0.37 liter at 30% by weight) within a double jacket mixer M kept at low temperature between -9 ° C and -11 ° C. Homogenization is ensured by magnetic drive.
- N-aminopiperidine is carried out in a single-phase medium in a stirred tubular reactor (R2), under scanning of argon or nitrogen.
- the NH 2 CI / NaOH mixture obtained (2.37 liters) and the piperidine solution (2.36 liters at 66% by weight) are introduced simultaneously (under argon or nitrogen) continuously into the reactor R2 with an adequate flow rate for have a piperidine to monochloramine molar ratio of approximately 8 and a titer of sodium hydroxide in the reaction medium at the end of the reaction equal to 0.3 mol.L "1.
- the reaction temperature is maintained at approximately 55 ° C.
- reaction mixture After 30 seconds of reaction, the reaction mixture then undergoes a degassing operation to remove the ammonia contained in the solution
- the reaction solution is first of all freed from the ammonia by stripping (distillation column CD1, recovery is obtained at the head about 62 g of ammonia) then about 4.6 kg of the ammonia-free solution are distilled at 92.2 ° C. at atmospheric pressure (CD2 distillation column) to remove the unreacted amine, piperidine.
- CD2 distillation column atmospheric pressure
- the piperidine is obtained at the top of the column in the form of an aqueous solution of composition of approximately 66% by weight in amine (approximately 2 kg). This solution is then recycled and immediately re-injected into R2, without additional treatment ( Figure 1: dotted arrow).
- the reaction solution containing the hydrazine (recovered at the bottom of the CD2 column, approximately 2.7 kg) is treated by addition of solid sodium hydroxide under cooling and under scanning of argon, to separate the N - aminopiperidine in an organic phase titrating nearly 70 to 80% hydrazine at 80 ° C.
- the mass titer of anhydrous soda injected is preferably between 15 and 30% by weight.
- This organic phase is thus recovered, titrating nearly 92% of hydrazine and an aqueous phase comprising water and the salts (NaCl, NaOH).
- the concentrated solution of hydrazine (organic phase) can then be used directly or distilled under reduced pressure (CD3 distillation column).
- N-aminopiperidine After distillation under reduced pressure, N-aminopiperidine is obtained with a degree of purity greater than 99.5%. The hydrazine yield relative to the piperidine consumed is greater than 92%.
- the reaction fluid from RI (2 liters) with a titer greater than 1 mol.L "1 in monochloramine is introduced into a mixer M fed continuously by a 30% sodium hydroxide solution (flow rate of 1.75 mL / min).
- a thermostatic jacket allows the temperature in the mixer to be set at -10 ° C.
- the synthesis of N-aminopiperidine is carried out by means of an agitated tubular agitator R2 and under scanning of argon.
- the alkalized monochloramine (2.35 liters), coming from the enclosure of the mixture M, and the amino reagent are introduced simultaneously at the base of the reactor by means of metering pumps.
- the present variant is characterized in that an amount of hydroxide of hydroxide is added to the homogeneous reaction liquor (4.04 liters). sodium between 13 and 30% under cooling so that the temperature does not exceed 60 ° C.
- N-aminopiperidine then requires two successive stages: recovery of the piperidine which has not reacted by distillation of the organic phase at atmospheric pressure under argon. concentrated amine solution at 66% by weight (1 ") at a temperature from 92.2 ° C until the water is used up, then about 600 g of anhydrous piperidine (1 ') at a temperature of 105 ° C (distillation column CD1').
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0314795A FR2864081B1 (fr) | 2003-12-17 | 2003-12-17 | Procede de synthese de derives de cycloalkyl-hydrazines exocycliques et de derives d'heterocycloalkyl-hydrazines exocycliques. |
PCT/FR2004/003288 WO2005058852A1 (fr) | 2003-12-17 | 2004-12-17 | Procede de synthese de derives de cycloalkyl-hydrazines exocycliques et de derives d’heterocycloalkyl-hydrazines exocycliques |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1699770A1 true EP1699770A1 (fr) | 2006-09-13 |
Family
ID=34630239
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP04816423A Withdrawn EP1699770A1 (fr) | 2003-12-17 | 2004-12-17 | Procede de synthese de derives de cycloalkyl-hydrazines exocycliques et de derives d'heterocycloalkyl-hydrazines exocycliques |
Country Status (8)
Country | Link |
---|---|
US (1) | US7879999B2 (fr) |
EP (1) | EP1699770A1 (fr) |
JP (1) | JP4926718B2 (fr) |
KR (1) | KR101090539B1 (fr) |
CN (1) | CN100528853C (fr) |
CA (1) | CA2550080C (fr) |
FR (1) | FR2864081B1 (fr) |
WO (1) | WO2005058852A1 (fr) |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2808439A (en) * | 1957-10-01 | Preparation of substituted chloramines | ||
US1095040A (en) * | 1912-09-10 | 1914-04-28 | Charles A Stevens | Coin-controlled height-indicating machine. |
US2806851A (en) * | 1954-03-25 | 1957-09-17 | Univ Ohio State Res Found | Substituted hydrazines |
US2901511A (en) * | 1956-03-22 | 1959-08-25 | Grace W R & Co | Substituted hydrazine process |
GB1095040A (en) * | 1966-04-01 | 1967-12-13 | Fmc Corp | Hydrazine derivatives |
DE2440238C3 (de) * | 1974-08-22 | 1981-11-19 | Hoechst Ag, 6000 Frankfurt | Verfahren zur Herstellung von organisch substituierter Hydrazine |
FR2610321B1 (fr) * | 1987-02-04 | 1989-04-07 | Oril Sa | Nouveau procede de synthese du n-amino aza-3 bicyclo (3, 3, 0) octane |
FR2651776B1 (fr) | 1989-09-13 | 1991-10-25 | Poudres & Explosifs Ste Nale | Procede de synthese de monomethylhydrazine en solution aqueuse. |
FR2663324B1 (fr) * | 1990-06-14 | 1992-09-04 | Adir | Nouveau procede de preparation industrielle du 4-chloro 3-sulfamoyl n-(2,3-dihydro 2-methyl 1h-indol-1-yl) benzamide. |
DE4138142C2 (de) * | 1991-11-20 | 1996-04-25 | Cassella Ag | Verfahren zur Herstellung von 1-Amino-2,6-dimethylpiperidin |
FR2846646B1 (fr) * | 2002-11-04 | 2005-01-21 | Isochem Sa | Procede de synthese de la monochloramine |
FR2864078B1 (fr) * | 2003-12-17 | 2006-02-10 | Isochem Sa | Procede de synthese en continu de monoalkyl hydrazines a groupe alkyle fonctionnalise |
FR2874013B1 (fr) * | 2004-08-05 | 2006-09-29 | Sanofi Synthelabo | Procede de preparation de la n-aminopiperidine et de ses sels |
-
2003
- 2003-12-17 FR FR0314795A patent/FR2864081B1/fr not_active Expired - Fee Related
-
2004
- 2004-12-17 JP JP2006544502A patent/JP4926718B2/ja not_active Expired - Fee Related
- 2004-12-17 EP EP04816423A patent/EP1699770A1/fr not_active Withdrawn
- 2004-12-17 US US10/583,284 patent/US7879999B2/en not_active Expired - Fee Related
- 2004-12-17 CN CNB2004800376391A patent/CN100528853C/zh not_active Expired - Fee Related
- 2004-12-17 KR KR1020067014401A patent/KR101090539B1/ko not_active IP Right Cessation
- 2004-12-17 WO PCT/FR2004/003288 patent/WO2005058852A1/fr active Application Filing
- 2004-12-17 CA CA2550080A patent/CA2550080C/fr not_active Expired - Fee Related
Non-Patent Citations (1)
Title |
---|
See references of WO2005058852A1 * |
Also Published As
Publication number | Publication date |
---|---|
JP4926718B2 (ja) | 2012-05-09 |
JP2007514723A (ja) | 2007-06-07 |
US7879999B2 (en) | 2011-02-01 |
FR2864081B1 (fr) | 2006-04-28 |
WO2005058852A1 (fr) | 2005-06-30 |
KR20070022639A (ko) | 2007-02-27 |
CN100528853C (zh) | 2009-08-19 |
CA2550080A1 (fr) | 2005-06-30 |
FR2864081A1 (fr) | 2005-06-24 |
KR101090539B1 (ko) | 2011-12-08 |
CN1894228A (zh) | 2007-01-10 |
CA2550080C (fr) | 2012-07-31 |
US20070249829A1 (en) | 2007-10-25 |
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