GB2152931A - Benzamide derivatives - Google Patents
Benzamide derivatives Download PDFInfo
- Publication number
- GB2152931A GB2152931A GB08501246A GB8501246A GB2152931A GB 2152931 A GB2152931 A GB 2152931A GB 08501246 A GB08501246 A GB 08501246A GB 8501246 A GB8501246 A GB 8501246A GB 2152931 A GB2152931 A GB 2152931A
- Authority
- GB
- United Kingdom
- Prior art keywords
- hydroxy
- formula
- benzamide
- compound
- process according
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a process for the preparation of 2-hydroxy-5-{1-hydroxy-2-[(1-methyl-3-phenylpropyl)-amino]ethyl}benzamide of the formula <IMAGE> and pharmaceutically acceptable acid addition salts thereof which comprises hydrogenating 2-hydroxy-5-{1-hydroxy-2-[(1-phenyl-but-1-ene-3-ylidene)imino]ethyl}be nzamide of the formula <IMAGE> and, if desired, converting the compound of the formula I thus obtained into a pharmaceutically acceptable acid addition salt. The new compound of the formula V may be prepared by reacting the compound of the formula <IMAGE> with 1-phenyl-2-butene-3-one of the formula <IMAGE> The compound of the formula II may be, in turn, prepared by catalytic hydrogenation of the compound of the formula <IMAGE>
Description
SPECIFICATION
Process for the preparation of a benzamide derivative
This invention relates to a process for the preparation of a benzamide derivative. More particularly, it is concerned with a new and improved process for the preparation of 2-hydroxy-5-(1 -hydroxy-2-[1 -methyl-3phenylpropyl)-amino]ethyl)benzamide and pharmaceutically acceptable acid addition salts thereof.
It is known that 2-hydroxy-5-(1-hydroxy-2-[1-methyl-3-phenylpropyl)-amino]ethyl)benzamide is a useful and wide-spread alpha- and beta-blocking hypotensive agent.
In the prior art a number of procedures are disclosed for the preparation of 2-hydroxy-5-(1 -hydroxy-2-[1 - methyl-3-phenylpropyl)emino]ethyl)benzamide. According to DOS No. 2,032,642 2-hydroxy-5cetylbenzamide is brominated, the',' -bromoacetyl derivative thus obtained is reacted with N-benzyl-N-(1methyl-3-phenylpropyl)amine and the keto group of the 2-hydroxy-5-(2-[N-benzyl-N-(1 -methyl-3phenylpropyl)-amino]acetyl)benzamide is reduced by catalytic hydrogenation while the protecting N-benzyl group is cleaved to yield 2-hydroxy-5- (1 -hydroxy-2-[1 -methyl-3-phenylpropyl)amino]ethyl)-benzamide.
The drawback of this process is that the end-product is obtained by means of a synthesis comprising many steps and in low yields. Moreover, the N-benzyl-N-(1 -methyl-3-phenylpropyl)amine component can be produced only in a multistep synthesis in a complicated manner, too.
According to an other process disclosed in DOS No. 2,032,642 2-hydroxy-5-(bromoacetyl)benzamide is reacted with N,N-dibenzylamine and the 2-hydroxy-5-(N,N-dibenzylglycyl)-benzamide of the formula
obtained is reacted with 1-phenyl-3-butanone under reducing conditions, The yields achieved are medium. A further disadvantage of this method resides in the fact that 1 -phenyl-3-butanone is not available on industrial scale and in the prior art no economical industrial scale manufacturing process of the said compound is disclosed.
According to a further method of said DOS 5-82-amino-1-hydroxyethyl)salicylamide is reacted with 1-phenyl-3-butanone in ethnolic solution under reducing conditions to give the desired compound 2-hydroxy-5-(1 -hydroxy-2-[1 -methyl-3-phenylpropyl)amino]ethyl)benzamide.
In the corresponding example, however, no yield is given. A drawback of this method is, as it was already mentioned above, that 1-phenyl-3-butanone starting material is not available on industrial scale.
In Belgian patent No. 840,779 and DOS No. 2,616,403 a process for the preparation and separation of diastereo-isomers of 2-hydroxy-5-(1 -hydroxy.2-[1 -methyl-3-phenyl-propyl)amino]ethyl)benzamide is disclosed. In the methods described therein as a result of the formation of the chiral centrum the number of reaction steps is increased, and the total yield of the synthesis is rather low.
According to the general formulae of Hungarian patent No. 165,291 2-hydroxy-5-(1 -hydroxy-2-[1 -methyl-3- phenylpropyl)-amino]ethyl)benzamide may be prepared by condensing 2-hydroxy-5-glyoxylylbenzoic acid ester with 1-phenyl-3-butylamine and subjecting the Schiff base thus obtained to catalytic hydrogenation. In the patent specification, however, no example is disclosed for the preparation of 2-hydroxy-5-(1-hydroxy-2- [1 -methyl-3-phenylpropyl)amino]ethyl)benzamide.
It is the object of the present invention to elaborate a process for the preparation of 2-hydroxy-5-(1hydroxy-2-[1-methyl-3-phenylpropyl)amino]ethyl)benzamide which eliminates the above drawbacks of the known methods, provides higher yields, is readily feasible on industrial scale production nd uses easily available starting materials.
It has been found that 2-hydroxy-5-(1 -hydroxy-2-[1 -methyl-3-phenylpropyl)amino]ethyl)benzamide of the formula
may be prepared in a more simple and economical manner from 2-hydroxy-5-(1-hydroxy-2-[1-phenyl-but-1- ene-3-ylidene)-imino]ethyl)benzamide of the formula
According to the present invention there is provided a process for the preparation of 2-hydroxy-5-(1 - hydroxy-2-[1-methyl-3-phenylpropyl)amino[ethyl)benzamide of the formula i and pharmaceutically acceptable acid addition salts thereof which comprises hydrogenating 2-hydroxy-5-(1 -hydroxy-2-[1 -phenyl-but-1ene-3-ylidene)imino]ethyl)benzamide of the formula V end, if desired, converting the compound of the formula I thus obtained into a pharmaceutically acceptable acid addition salt.
The reduction of the Schiff base of the formula V may be carried out by catalytic hydrogenation. As catalyst preferably palladium, platinum, nickel or an Adams catalyst may be used. The catalyst may also be applied on a carrier (e.g. charcoal, barium sulfate). Hydrogenation may be carried out at a temperature between 10"C and 40"C, preferably at a temperature of about 20-30"C, and under a pressure of 1-10 atm., preferably 2-4 atm. One may particularly advantageously work at 25"C and under a pressure of 3 atm. The reduction may be carried out in an inert organic solvent. As reaction medium preferably an ether (e.g. diethyl ether, dioxane or tetrehydrofuran) or an alcohol (e.g. methanol or ethanol), particularly tetrahydrofuran may be used.In the course of the reaction two equivalents of hydrogen are consumed and both the azomethine bond and carbon-carbon double bond are saturated. The reaction may be accomplished in the presence of a small amount of an organic acid (e.g. glacial acetic acid). The yields achieved are almost theoretic.
The reaction mixture may be worked up by methods known per se. One may preferably proceed by filtering off the catalyst and evaporating the filtrate. The hydrochloride may be isolated by adding anhydrous ethanolic hydrogen chloride or a mixture of concentrated hydrochloric acid and ethanol to the hydrogenated filtrate.
The starting material of the formula V is a new compound and may be prepared by reacting 2-hydroxy-5-(1 -hydroxy-2-aminoethyl)benzamide of the formula
with 1-phenyl-but-1-ene-3-one of the formula
The reaction may be carried out in an inert organic solvent. As reaction medium preferably an ether (e.g.
diethyl ether, dioxane ortetrahydrofuran), alcohol (e.g. methanol or ethanol) or a aromatic hydrocarbon (e.g.
benzene, toluene or xylene), particularly tetrahydrofuran may be used. The reaction may be accomplished at a temperature between 25-1 00 C, preferably at a temperature of about 40"C. The reaction may optionally be carried out in the presence of a base (e.g. triethyl amine or morpholine).
The compound of the formula V thus obtained may either be isolated or subjected to catalytic hydrogenation in situ without isolation.
According to a form of realization of the process of the present invention the compound of the formula II prepared by catalytic hydrogenation of the compound of the formula
is used. One may work preferably by subjecting a compound of the formula VI to catalytic hydrogenation, reacting the compound of the formula II thus formed in situ with the compound of the formula Ill and hydrogenating the compound of the formula V thus formed without isolation.
According to a further form of realization of the process of the present invention the compound of the formula II prepared by catalytic hydrogenation of the compound of the formula IV is used. One may proceed preferably by subjecting the compound of the formula IV to catalytic hydrogenation, reacting the compound of the formula II thus formed in situ with a compound of the formula Ill and hydrogenating the compound of the formula V thus formed without isolation.
The two latter forms of realization of the process of the present invention may be carried out preferably at an elevated temperature, preferably at 50-70"C and under a pressure between 1 and 100 atm., preferably under a pressure of about 50 atm. The reaction may be carried out in an inert organic solvent. As reaction medium preferably an alcohol (e.g. methanol or ethanol) may be used. The reaction mixture may also contain an acid (e.g. glacial acetic acid). As catalyst e.g. palladium, platinum, nickel or Adams catalyst may be used. The catalyst may be applied onto a carrier, e.g. charcoal, barium sulfate, etc., if desired.
The major advantage of the process of the present invention is that the starting materials used for the preparation of the compound of the formula V may be prepared from materials (e.g. benzal acetone) readily available on industrial scale, the process is readily feasible and economical on industrial scale too and the yields are high.
Without limiting the scope of the invention by theoretical considerations we presume that this is due to the fact that because of conjugation the keto group of 1-phenyl-but-1-ene-3-one (benzal acetone) used in the process of the present invention is more reactive than the keto group of 1 -phenyl-butan-3-one applied in the process disclosed in DOS No. 2,032,642.For this reason the compound of the formula Ill reacts with the 2-hydroxy-5-(1-hydroxy-2-amino-ethyl)-benzamide of the formula II to give the corresponding 2-hydroxyd- (1 -hydroxy-2-[1 -phenyl-but-1 -ene-3-ylidene)imino]ethyl)-benzamide much more easily than the corresponding intermediate is formed in the process described in DOS No. 2,032,642, namely 2-hydrosy-5-(1-hydroxy-2 [1-phenyl-but-3-ylidene)imino]ethyl]benzamide or 2-hydroxy-5-(1 -keto-2-[1 -phenyl-but-3-ylidene)- imino[ethyl)benzamide.
Further details of the process of the invention are to be found in the following Examples without limiting the scope of protection by the said Examples.
Example 1 Preparation of 2-hydroxy-5-( 1 2-hydroxy-5-(1 -hydroxy-2-[1-phenyl-but-1-ene-3-ylidene)iminojethyl)benzamide 2.30 g. (10 millimoles) of 2-hydroxy-5-(1-hydroxy-2-aminoethyl)benzamide hydrochloride and 1.46 g. (10 millimoles) of 1-phenyl-but-1-ene-3-one are admixed with 10 ml. of tetrahydrofuran whereupon under further stirring and ice-cooling 1.20 ml. of triethyl amine are added dropwise at a temperature of 10-1 5 C. The addition having been completed the reaction mixture is stirred at room temperature for further 5 hours and the precipitated triethyl amine hydrochloride is filtered off. From the filtrate the 2-hydroxy-5-(1 -hydroxy-2-( 1 - phenyl-but-1 -ene-3-ylidene)imino]-ethyl)benzamide is isolated by column chromatography on silice gel.
Thus 1.56 g. of the desired compound are obtained, yield 48%, m.p.: 142-146"C.
Example 2
Preparation of 2-hydroxy-5-(1-hydroxy-2-[1-phenyl-but-1-ene-3-ylidene)imino]ethyl)benzamide 2.30 g. (10 millimoles) of 2-hydroxy-5-(1-hydroxy-2-aminoethyl)benzamide hydrochloride and 1-46 g. (10 millimoles) of 1-phenyl-but-1-ene-3-one are admixed with 10 ml. of tetrahydrofuran, whereupon under further stirring and ice-cooling 4 ml. of morpholine are added dropwise at a temperature of 10-1 5"C. The reaction mixture is stirred at room temperature for a further period of 5 hours, the precipitated morpholine hydrochloride is filtered off and the filtrate is heated to boiling for 3 hours. From the filtrate the desired compound is isolated by column chromatography on silica gel. Thus 2.05 g. of the desired compound are obtained, yield 63 %. M.p.: 142-145 "C.
Example 3
Preparation of 2-hydroxy-5-( 1 -hydroxy-2-[1 -methyl-3-phenyl-propyl )amino]ethyl )benzamide hydrochloride
3.249 (10 millimoles) of 2-hydroxy-5-(1 -hydroxy-2-[1 -phenyl-but-1 -ene-3-ylidene)imino]ethyl)benzamide prepared according to Example 1 or 2 are dissolved in 25 ml. of tetra-hydrofuran, whereupon 0.5 g. of a 10 palladium-on-charcoal catalyst are added and the mixture is hydrogenated at a temperature of 25"C under a pressure of 3 atm. The reduction having been terminated the catalyst is filtered off and to the filtrate 5 ml. of ethanol containing 20% of hydrochloric acid are added.The precipitated white crystals are filtered off and washed with ethanol. Thus 3.46 g. of the desired compound are obtained, yield 95 /O, m.p.: 188-189"C.
Example 4
Preparation of 2-hydroxy-5-(1 -hydroxy-2-[1 .methyl-3-phenyl-propyl)amino]ethyl)benzamide hydrochloride
To a solution of 3.74 g. (10 millimoles) of 2-hydroxy-5-(N,N-dibenzylglycyl)benzamide, 1.46 g. (10 millimoles) of 1-phenyl-but-1-ene-3-one and 50 ml. of methanol 1.0 ml. of glacial acetic acid, 1.0 g. of a 10 % palladium-on-charcoal catalyst and 0.1 g. of platinum oxide (Adams catalyst) are added. The rection mixture is hydrogenated at a temperature of 60"C and under a pressure of 50 atm. The catalyst is filtered off and the filtrate is evaporated to a small volume. To the residue 3 ml. of propanol saturated with hydrogen chloride and 5 ml. of ethyl acetate are added. On standing crystals precipitate which are filtered off and washed.Thus 2.62 g. of the desired compound are obtained, yield: 72% m.p.: 187-190"C.
Example 5
Preparation of 2-hydroxy-5-(1 -hydroxy-2-[1 -methyl-3-phenyl-propyl)amino]ethyl)benzamide hydrochloride
To a solution of 3.76 g. (10 millimoles) of 2-hydroxy-5-[l -hydroxy-2-(dibenzylamino)ethyl] benzamide and 1.46 g. (10 millimoles) of 1-phenyl-but-1-ene-3-one in 50 ml. of methanol 1.0 ml. of glacial acetic acid, 1.0 g. of a 10 % palladium-on-charcoal catalyst and 0.1 g. of platinum oxid (Adams catalyst) are added and the reaction mixture is hydrogenated at a temperature of 60"C and under a pressure of 50 atm. The reaction mixture is worked up and the product isolated according to Example 4. Thus 2.77 g. of the desired product are obtained, yield 76%, m.p.: 188-1 89 C.
Claims (15)
1. Process for the preparation of 2-hydroxy-5-( 1 -hydroxy-2-[1 -methyl-3 phenylpropyl)amino]ethyl)benzamide of the formula
and pharmaceutically acceptable acid addition salts thereof which comprises hydrogenating 2-hydroxy-5-(1 hydrnxy-2-[1 -phenyl-but-1 -ene-3-ylidene)imino]ethyl)benzamide of the formula
and, if desired, converting the compound of the formula I thus obtained into a pharmaceutically acceptable acid addition salt.
2. Process according to claim 1 which comprises carrying out the hydrogenation in the presence of a catalyst.
3. Process according to claim 2 which comprises using a palladium, platinum or nickel catalyst or a mixture thereof.
4. Process according to any of claims 1 to 3 which comprises carrying out the reaction in the presence of an insert organic solvent.
5. Process according to claim 4 which comprises using an ether or alcohol as solvent.
6. Process according to any of claims 1 to 5 which comprises carrying out the reaction at a temperature between 10"C and 40"C, preferably at a temperature of about 20 to 30"C, and under a pressure of 1 to 10 atm., preferably 2 to 4 atm.
7, Process according to claim 1 which comprises using as starting material a compound of the formula V prepared by reacting 2-hydroxy-5-(1 -hydroxy-2-amincethyl)benzamide of the formula
with 1 -phenyl-but-1 -ene-3-one of the formula
8. Process according to claim 7 which comprises carrying out the reaction to an inert organic solvent.
9. Process according to claim 8 which comprises using an ether, alcohol or aromatic hydrocarbon as solvent.
10. Process according to claim 7 which comprises using 2-hydroxy-5-(1-hydroxy-2aminoethyl)benzamide of the formula II prepared in situ by catalytic hydrogenation of 2-hydroxy-5-[1 - hydroxy-2-(N,N-dibenzylaminolethyl]benzamide of the formula
reacting the compound of the formula II without isolation in situ with the compound of the formula III and subjecting the compound of the formula V thus obtained without isolation in situ, to hydrogenation.
11. Process according to claim 7 which comprises using 2-hydroxy-5-(1-hydroxy-2amincethyl)benzamide of the formula II prepared in situ by catalytic hydrogenation of 2-hydroxy-5-(N,Ndibenzylglycyl)benzamide of the formula
reacting the compound of the formula II without isolation in situ, with the compound of the formula Ill and subjecting the compound of the formula V thus formed without isolation in situ, to hydrogenation.
12. 2-Hydroxy-5-(1 -hydroxy-2-(1 -phenyl-but-1 -ene-3-ylidene)iminojethyl)benzamide of the formula
13. A process as claimed in claim 1 substantially as hereinbefore described in any one of Examples 3 to 5.
14. A process as claimed in claim 1, wherein the compound of the general formula V is substantially as hereinbefore described in Example 1 or 2.
15. 2-hydroxy-5-(1 -hydroxy-2-[(1 -methyl-3-phenyl-propyl)amino[ ethyl)benzamide or a pharmaceutically acceptable acid addition salt thereof made by a process as claimed in any one of claims 1 to 11, 13 and 14.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU23484A HU190867B (en) | 1984-01-20 | 1984-01-20 | Process for preparing 2-hydroxy-5-/1-hydroxy-2-/1-methyl-3-phenyl-propyl/-amino/ethyl/-benzamide and pharmaceutically acceptable salts thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8501246D0 GB8501246D0 (en) | 1985-02-20 |
| GB2152931A true GB2152931A (en) | 1985-08-14 |
| GB2152931B GB2152931B (en) | 1987-03-18 |
Family
ID=10948617
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB08501246A Expired GB2152931B (en) | 1984-01-20 | 1985-01-18 | Benzamide derivatives |
Country Status (18)
| Country | Link |
|---|---|
| JP (1) | JPS60231639A (en) |
| AT (1) | AT390612B (en) |
| CA (1) | CA1239938A (en) |
| CH (1) | CH662810A5 (en) |
| CS (1) | CS249536B2 (en) |
| DD (1) | DD228245A5 (en) |
| DE (1) | DE3501582A1 (en) |
| DK (1) | DK26185A (en) |
| ES (1) | ES8608481A1 (en) |
| FI (1) | FI83635C (en) |
| FR (1) | FR2558465B1 (en) |
| GB (1) | GB2152931B (en) |
| HU (1) | HU190867B (en) |
| NL (1) | NL8500119A (en) |
| NO (1) | NO165918C (en) |
| PT (1) | PT79844B (en) |
| SE (1) | SE8500236L (en) |
| SU (1) | SU1521281A3 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1247370A (en) * | 1968-12-31 | 1971-09-22 | Allen & Hanburys Ltd | Glyoxals and production thereof |
| ZA794872B (en) * | 1978-09-20 | 1980-11-26 | Schering Corp | A phenylalkylaminoethylsalicylamide,its preparation and pharmaceutical compositions containing it |
-
1984
- 1984-01-20 HU HU23484A patent/HU190867B/en not_active IP Right Cessation
- 1984-12-17 CH CH598584A patent/CH662810A5/en not_active IP Right Cessation
-
1985
- 1985-01-18 SU SU853837675A patent/SU1521281A3/en active
- 1985-01-18 JP JP597885A patent/JPS60231639A/en active Pending
- 1985-01-18 AT AT11685A patent/AT390612B/en not_active IP Right Cessation
- 1985-01-18 GB GB08501246A patent/GB2152931B/en not_active Expired
- 1985-01-18 PT PT7984485A patent/PT79844B/en unknown
- 1985-01-18 FR FR8500702A patent/FR2558465B1/en not_active Expired
- 1985-01-18 DE DE19853501582 patent/DE3501582A1/en not_active Withdrawn
- 1985-01-18 DD DD27264985A patent/DD228245A5/en not_active IP Right Cessation
- 1985-01-18 CA CA000472445A patent/CA1239938A/en not_active Expired
- 1985-01-18 FI FI850229A patent/FI83635C/en not_active IP Right Cessation
- 1985-01-18 DK DK26185A patent/DK26185A/en not_active Application Discontinuation
- 1985-01-18 CS CS37785A patent/CS249536B2/en unknown
- 1985-01-18 NO NO850225A patent/NO165918C/en unknown
- 1985-01-18 NL NL8500119A patent/NL8500119A/en not_active Application Discontinuation
- 1985-01-18 ES ES540121A patent/ES8608481A1/en not_active Expired
- 1985-06-06 SE SE8500236A patent/SE8500236L/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2558465A1 (en) | 1985-07-26 |
| NL8500119A (en) | 1985-08-16 |
| FI83635B (en) | 1991-04-30 |
| FR2558465B1 (en) | 1988-08-26 |
| GB2152931B (en) | 1987-03-18 |
| NO165918C (en) | 1991-05-02 |
| CH662810A5 (en) | 1987-10-30 |
| NO165918B (en) | 1991-01-21 |
| FI850229A0 (en) | 1985-01-18 |
| AT390612B (en) | 1990-06-11 |
| ES540121A0 (en) | 1986-07-16 |
| GB8501246D0 (en) | 1985-02-20 |
| DD228245A5 (en) | 1985-10-09 |
| PT79844B (en) | 1986-10-23 |
| DK26185A (en) | 1985-07-21 |
| ATA11685A (en) | 1989-11-15 |
| PT79844A (en) | 1985-02-01 |
| SE8500236L (en) | 1985-07-21 |
| JPS60231639A (en) | 1985-11-18 |
| HUT36779A (en) | 1985-10-28 |
| SE8500236D0 (en) | 1985-01-18 |
| CS249536B2 (en) | 1987-03-12 |
| NO850225L (en) | 1985-07-22 |
| FI850229L (en) | 1985-07-21 |
| SU1521281A3 (en) | 1989-11-07 |
| DK26185D0 (en) | 1985-01-18 |
| HU190867B (en) | 1986-11-28 |
| CA1239938A (en) | 1988-08-02 |
| ES8608481A1 (en) | 1986-07-16 |
| DE3501582A1 (en) | 1985-08-01 |
| FI83635C (en) | 1991-08-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| SU1333234A3 (en) | Method of producing the derivatives of n-phenylbenzamide or salts thereof | |
| US5434304A (en) | Process for preparing formoterol and related compounds | |
| DE69109514T2 (en) | 4- (4-alkoxyphenyl) -2-butylamine derivatives and their production processes. | |
| US4118417A (en) | Process for resolving cis-1-substituted phenyl-1,2-cyclopropanedicarboxylic acids | |
| HU190875B (en) | Process for preparing derivatives of spiro-2-aza-alkane-3-carboxylic acids | |
| EP0550612B1 (en) | New process for preparing formoterol and related compounds | |
| KR19990013522A (en) | Process for preparing substituted perhydroisoindole | |
| US4824953A (en) | Multi-step process for producing 5-hydroxy-N-(6-oxo-piperidyl-methyl)-2-(2,2,2-trifluoro-ethoxy)-benzamide and derivatives | |
| NO177531B (en) | Process for the preparation of 1- (aminomethyl) cyclohexanacetic acid, as well as an intermediate for use in this process | |
| US5371237A (en) | Process for the production of 4-hydroxy-2-oxopyrrolidin-1-yl-acetamide | |
| EP0128007A2 (en) | Phenyl tetrahydronaphthylcarboxylate derivatives | |
| US4536601A (en) | Optically active N-substituted phenylalaninols and use thereof | |
| GB2152931A (en) | Benzamide derivatives | |
| US4150030A (en) | 3-Acyl-4-ethyl-2-oxazolones and oxazolidinones | |
| US4855455A (en) | Preparation of amino acid derivatives | |
| JP2810465B2 (en) | Method for producing N-methyl-4-t-butylbenzylamine | |
| CA1158249A (en) | Preparation of 1h-pyrrol-2-acetic acid esters | |
| US2727040A (en) | Tertiary-aminoalkyl 4-alkylamino-2-hydroxybenzoates, their salts and preparation thereof | |
| KR800000537B1 (en) | Process for the preparation of amin-pheny-etahnolamines | |
| AU611603B2 (en) | Process and intermediates for isopropyl 3s-amino-2r-hydroxy- alkanoates | |
| JPS5995286A (en) | Imidazo[4,5-c]pyridine-6-carboxylic acid derivative | |
| AT347473B (en) | PROCESS FOR THE PREPARATION OF NEW MORPHOLINE COMPOUNDS AND THEIR NON-TOXIC SALT | |
| EP0140646A1 (en) | Process for producing 9-carbamoyl fluorene derivatives | |
| DD262021A1 (en) | METHOD FOR THE PRODUCTION OF HYDROCHLORIDES OF LENGTH-STRINGED ALKYLESTER RINGS-SUPPORTED DL-PHENYLAMINOSAURES | |
| CS214776B2 (en) | Method of making the derivatives of the phenylacetic acid |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |