EP0825976A1 - Verfahren zur herstellung von n-methyl-2-(3,4-dimethoxy-phenyl)-ethylamin - Google Patents
Verfahren zur herstellung von n-methyl-2-(3,4-dimethoxy-phenyl)-ethylaminInfo
- Publication number
- EP0825976A1 EP0825976A1 EP96919667A EP96919667A EP0825976A1 EP 0825976 A1 EP0825976 A1 EP 0825976A1 EP 96919667 A EP96919667 A EP 96919667A EP 96919667 A EP96919667 A EP 96919667A EP 0825976 A1 EP0825976 A1 EP 0825976A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- methyl
- preparation
- palladium
- dimethoxyphenyl
- ethylamine
- 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.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
- B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
Definitions
- the present invention relates to a process for the preparation of N-methyl-2- (3,4-dimethoxyphenyl) ethylamine (N-methylhomoviratrylamine) by reacting 3,4-dimethoxyphenylmethyl nitrile (veratryl cyanide) with methylamine or a substituted Me ⁇ thylamine, the substituent being a group which can be split off under the reaction conditions, and hydrogen in the presence of a supported catalyst which contains copper chromite, an element from Group IB or VIII of the Periodic Table of the Elements or mixtures thereof, optionally in the presence of water elevated temperatures hydrogenated.
- DE-A-33 38 681 discloses the catalytic hydrogenation of veratryl cyanide with a ten-fold molar excess of methylamine over a nickel catalyst. As a by-product, the homoveratrylamine is obtained with over 3% selectivity, which must be removed by adding benzaldehyde.
- R 1 is hydrogen, benzyl or tert-butyl, and hydrogen in the presence of a supported catalyst which contains 0.05 to 50% by weight of copper chromite, copper, silver, gold, iron, cobalt, nickel, ruthenium, rhodium, palladium Contains, osmium, iridium, platinum or mixtures thereof, optionally hydrogenated in the presence of water at temperatures from 50 to 200 ° C and pressures from 1 to 300 bar.
- the method according to the invention can be carried out as follows:
- 3,4-Dimethoxyphenylmethylnitrile with a methylamine I and hydrogen can with 0 to 30 wt .-%, preferably 0.05 to
- a supported catalyst which contains copper chromite, an element from Group IB or VIII of the Periodic Table of the Elements or mixtures thereof batchwise or continuously, preferably in a pressure vessel or pressure reactor such as, for example, an autoclave or a tubular reactor, particularly preferably continuously in a tubular reactor, at temperatures from 20 to 200 ° C., preferably 50 to 180 ° C., particularly preferably 70 to 160 ° C. and pressures from 1 to 300 bar, preferably 30 to 300 bar, particularly preferably 50 and 270 bar and optionally with the addition of a solvent.
- Working up can be carried out according to methods known per se, for example by distillation.
- Particularly suitable methylamines I are methylamine itself and substituted methylamines I whose substituent is a group which can be split off under the reaction conditions, such as benzyl and tert. -Butyl, i.e. benzylmethylamine and tert. -Butyl-methylamine, preferably benzyl-methylamine.
- the benzyl or tert-butyl group can preferably be split off under the hydrogenation conditions, thermally or in the presence of inorganic or organic acids such as sulfuric acid, hydrochloric acid, methylsulfonic acid or acetic acid, or acidic catalysts such as ion exchangers or zeolites .
- the molar ratio of methylamine to 3,4-dimethoxyphenyl-methyl-nitrile is generally from 1: 1 to 15: 1, preferably from '1.5: 1 to 10: 1, more preferably 2: 1 to 5: 1.
- Suitable solvents are alcohols with 1 to 8 carbon atoms, preferably alcohols with 1 to 4 carbon atoms, N-substituted pyrrolidones such as N-methylpyrrolidone, ethers such as tetrahydrofuran, aromatic hydrocarbons such as benzene, toluene or the Xylenes, or the methylamine used itself. Particularly preferred are methanol, N-methylpyrrolidone, tetrahydrofuran, methylbenzylamine and methylamine.
- the copper chromite an element of
- Group IB or VIII of the Periodic Table of the Elements or mixtures thereof are those which contain copper chromite, copper, silver, gold, iron, cobalt, nickel, ruthenium, rhodium, palladium, osmium, iridium, platinum or mixtures thereof copper chromite, copper, palladium, platinum or their mixtures, particularly preferably palladium, platinum or their mixtures, in particular platinum, in a total content of 0.05 to 50% by weight, preferably 0.1 to 10% by weight .-%, particularly preferably 0.5 and 2 wt .-% on a carrier, preferably consist thereof.
- Suitable carriers are, for example, activated carbons, silicon carbide or oxides such as aluminum oxide, silicon dioxide, titanium dioxide, zirconium dioxide, zinc oxide, magnesium oxide or mixtures thereof, which are optionally doped with alkali and / or alkaline earth metal oxides, preferably ⁇ -aluminum oxide, silicon dioxide or aluminum - Minium oxide / silicon dioxide mixtures.
- the carriers can e.g. can be used as extrudates, pellets or tablets.
- the catalysts of the invention are generally prepared by processes known in the art, and can preferably be carried out using the process of pore impregnation.
- the metal precursors can be dissolved in an amount of water corresponding to the pore volume of the support, the support soaked with the solution and the catalyst then for example for 1 to 48 hours, preferably 12 to 24 hours, at temperatures of, for example, 80 to 170 ° C, preferably 100 to 150 ° C, are dried. The drying can be done dormant or moving.
- pore impregnation it is also possible to impregnate with an amount of solvent which is greater than the pore volume of the support (impregnation with excess solution).
- the dried catalyst can then be calcined, for example, for 0.5 to 10 hours, preferably 1 to 3 hours, generally in an air stream at a temperature between 300 and 700 ° C., preferably 400 and 600 ° C.
- Suitable metal precursors are metal salts such as nitrates, nitrosyl nitrates, halides, carbonates, carboxylates, acetylacetonates, chloro complexes, nitrite complexes or amine complexes, preferably nitrates, chlorides or chloro complexes.
- the metal precursors can be impregnated simultaneously or in succession.
- the catalyst is dried after each impregnation step for 1 to 48 h, preferably 12 to 24 h, at temperatures between 80 and 170 ° C., preferably 100 to 150 ° C.
- the order in which the active components are impregnated can be chosen as desired.
- N-methyl-2- (3,4-dimethoxyphenyl) ethylamine is an intermediate in the synthesis of the active ingredient verapamil (US Pat. No. 3,261,859).
- a vertical hydrogenation reactor (diameter: 16 mm; filling height: 600 mm; oil-heated double jacket), which was filled with 511 g (800 ml) of catalyst (0.5% by weight of palladium on aluminum oxide), was used in bottoms at 200 bar and 160 ° C. hourly 205 ml of a 28% solution of veratryl cyanide in methylbenzylamine (molar ratio 1: 3.7) were pumped. At the same time, you were running
- a vertical hydrogenation reactor (diameter: 27 mm; filling height: 1500 mm; oil-heated double jacket), which was filled with 800 ml of a catalyst consisting of 0.5% by weight of palladium on ⁇ -aluminum oxide as 4 mm strands, were in swamp mode at
- N-methyl-2- (3,4-dimethoxyphenyl) -ethylamine (N-methylhomoveratryl-20 amine) was obtained in a yield of 90% with quantitative conversion of
- Catalyst A 0.5% by weight of palladium on A1 2 0 3
- Catalyst B 1% by weight of platinum on A1 2 0 3
- 1613 g of an aluminum oxide carrier in the form of 4 mm extrudates with a liter weight of 560 g / 1, a pore volume of 0.68 cm 3 / g and a surface area of 203 m 2 / g were mixed with 1097 ml of an aqueous platinum (II) -Nitrate solution soaked and dried for 20 h at 40 120 ° C and calcined at 450 ° C for 3 h.
- II aqueous platinum
- Catalyst C 0.8% by weight of platinum on Si0 2 / Al 2 0 3
- II hydrochloric acid platinum
- Catalyst D 0.4% by weight Pd / 0.4% by weight Pt on Si0 / Al 2 0 3
- the silicon dioxide / aluminum oxide support described for the catalyst C was impregnated with 970 ml of a solution containing hydrochloric acid, palladium (II) chloride and platinum (II) chloride and dried at 120 ° C. for 20 hours and quiescent Calcined at 450 ° C for 3 h.
- Catalyst E 0.8% by weight of palladium on Si0 2 / Al 0 3
- the silicon dioxide / aluminum oxide support described for catalyst C was impregnated with 970 ml of a hydrochloric acid palladium (II) chloride solution and dried for 20 hours at 120 ° C. and calcined at 450 ° C. for 3 hours.
- Catalyst F 0.8% by weight of palladium on SiO 2 / Al 2 O 3
- the preparation was carried out analogously to catalyst E, but the impregnated catalyst was agitated in the rotary tube for 1 hour at 120 ° C. and calcined at 450 ° C. for 1 hour.
- Catalyst G 0.8% by weight of palladium on Si0 2
- NMP N-methylpyrrolidone
- HVA homoveratrylamine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1995118038 DE19518038A1 (de) | 1995-05-17 | 1995-05-17 | Verfahren zur Herstellung von N-Methyl-2-(3,4-dimethoxyphenyl)-ethylamin |
DE19518018 | 1995-05-17 | ||
DE1995118018 DE19518018A1 (de) | 1995-05-17 | 1995-05-17 | Verfahren zur Herstellung von N-Methyl-2-(3,4-dimethoxyphenyl)-ethylamin |
DE19518038 | 1995-05-17 | ||
DE1996106729 DE19606729A1 (de) | 1996-02-23 | 1996-02-23 | Verfahren zur Herstellung von N-Methyl-2-(3,4-dimethoxyphenyl)-ethylamin |
DE19606729 | 1996-02-23 | ||
PCT/EP1996/001861 WO1996036589A1 (de) | 1995-05-17 | 1996-05-04 | Verfahren zur herstellung von n-methyl-2-(3,4-dimethoxy-phenyl)-ethylamin |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0825976A1 true EP0825976A1 (de) | 1998-03-04 |
Family
ID=27215126
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP96919667A Ceased EP0825976A1 (de) | 1995-05-17 | 1996-05-04 | Verfahren zur herstellung von n-methyl-2-(3,4-dimethoxy-phenyl)-ethylamin |
Country Status (14)
Country | Link |
---|---|
US (1) | US5840981A (xx) |
EP (1) | EP0825976A1 (xx) |
KR (1) | KR19990014830A (xx) |
CN (1) | CN1184463A (xx) |
AU (1) | AU5813496A (xx) |
BR (1) | BR9608468A (xx) |
CZ (1) | CZ345597A3 (xx) |
EA (1) | EA000698B1 (xx) |
HU (1) | HUP9801069A3 (xx) |
MX (1) | MX9708720A (xx) |
PL (1) | PL323359A1 (xx) |
SK (1) | SK281665B6 (xx) |
TR (1) | TR199701373T1 (xx) |
WO (1) | WO1996036589A1 (xx) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE19756947A1 (de) * | 1997-12-22 | 1999-06-24 | Basf Ag | Verfahren zur Herstellung sekundärer Amine aus Nitrilen und primären Aminen |
DE19942300A1 (de) | 1999-09-04 | 2001-03-08 | Basf Ag | Verfahren zur Herstellung von Alkanolaminen mit verbesserter Farbqualität |
US20100019191A1 (en) * | 2006-12-15 | 2010-01-28 | Basf Se | Method for producing 1,2-ethylene glycol and 1,2-propylene glycol by means of the heterogeneously catalysed hydrogenolysis of a polyol |
US7538060B2 (en) * | 2007-02-14 | 2009-05-26 | Eastman Chemical Company | Palladium-copper chromite hydrogenation catalysts |
US20080194398A1 (en) * | 2007-02-14 | 2008-08-14 | Eastman Chemical Company | Ruthenium-copper chromite hydrogenation catalysts |
JP2010536913A (ja) * | 2007-08-29 | 2010-12-02 | ビーエーエスエフ ソシエタス・ヨーロピア | グリセリンからのアミンの製造方法 |
WO2009027249A2 (de) * | 2007-08-29 | 2009-03-05 | Basf Se | Verfahren zur herstellung von aminen aus zuckeralkoholen |
CN102203054B (zh) | 2008-11-05 | 2014-07-30 | 巴斯夫欧洲公司 | 生产n,n-取代的3-氨基丙-1-醇的方法 |
CN110452222B (zh) * | 2019-08-29 | 2020-10-16 | 杭州中美华东制药有限公司 | 一种富马酸沃诺拉赞的制备方法 |
CN114853728B (zh) * | 2022-05-07 | 2023-11-07 | 四川制药制剂有限公司 | 一种富马酸伏诺拉生片及其制备方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3338681A1 (de) * | 1983-10-25 | 1985-05-09 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von n-methylhomoveratrylamin |
IT1229214B (it) * | 1989-03-31 | 1991-07-25 | Alfa Wassermann S P A Contrada | Processo per la sintesi della n metil 3,4 dimetossifeniletilamina |
-
1996
- 1996-05-04 AU AU58134/96A patent/AU5813496A/en not_active Abandoned
- 1996-05-04 EA EA199700392A patent/EA000698B1/ru not_active IP Right Cessation
- 1996-05-04 KR KR1019970708174A patent/KR19990014830A/ko not_active Application Discontinuation
- 1996-05-04 MX MX9708720A patent/MX9708720A/es not_active IP Right Cessation
- 1996-05-04 BR BR9608468A patent/BR9608468A/pt not_active Application Discontinuation
- 1996-05-04 WO PCT/EP1996/001861 patent/WO1996036589A1/de not_active Application Discontinuation
- 1996-05-04 CZ CZ973455A patent/CZ345597A3/cs unknown
- 1996-05-04 CN CN96193949A patent/CN1184463A/zh active Pending
- 1996-05-04 PL PL96323359A patent/PL323359A1/xx unknown
- 1996-05-04 TR TR97/01373T patent/TR199701373T1/xx unknown
- 1996-05-04 EP EP96919667A patent/EP0825976A1/de not_active Ceased
- 1996-05-04 US US08/945,530 patent/US5840981A/en not_active Expired - Fee Related
- 1996-05-04 HU HU9801069A patent/HUP9801069A3/hu unknown
- 1996-05-04 SK SK1427-97A patent/SK281665B6/sk unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9636589A1 * |
Also Published As
Publication number | Publication date |
---|---|
KR19990014830A (ko) | 1999-02-25 |
EA199700392A1 (ru) | 1998-06-25 |
MX9708720A (es) | 1997-12-31 |
HUP9801069A3 (en) | 2000-06-28 |
AU5813496A (en) | 1996-11-29 |
SK281665B6 (sk) | 2001-06-11 |
CZ345597A3 (cs) | 1998-04-15 |
HUP9801069A2 (hu) | 1999-05-28 |
BR9608468A (pt) | 1998-12-29 |
TR199701373T1 (xx) | 1998-02-21 |
PL323359A1 (en) | 1998-03-30 |
US5840981A (en) | 1998-11-24 |
CN1184463A (zh) | 1998-06-10 |
EA000698B1 (ru) | 2000-02-28 |
SK142797A3 (en) | 1998-06-03 |
WO1996036589A1 (de) | 1996-11-21 |
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Legal Events
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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Effective date: 19971114 |
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AK | Designated contracting states |
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Effective date: 19990712 |
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STAA | Information on the status of an ep patent application or granted ep patent |
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18R | Application refused |
Effective date: 20010823 |