DE3501582A1 - METHOD FOR PRODUCING 2- (HYDROXY) -5- (1 '- (HYDROXY) -2' - (1 '' - (METHYL) -3 '' - (PHENYL) -PROPYLAMINO) -ETHYL) -BENZAMID AND 2- ( HYDROXY) -5- (1 '- (HYDROXY) -2' - (1 '' - (PHENYL) -BUT-1 '' - EN-3 '' - YLIDEN-IMINO) -AETHYL) -BENZAMIDE AND METHOD FOR PRODUCING THE SAME THE LAST - Google Patents

Abstract

The invention relates to a process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- [methyl] -3" - [phenyl] propylamino) ethyl] -benzamide of the formula I and its acid addition salts, in which a) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- [phenyl] -but-1" - en- 3 '' - ylidenemino) ethyl] benzamide of the formula is reduced or b) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- [benzyl] - amino) ethyl] benzamide of the formula or 2- [hydroxy] -5- [N, N-di- (benzyl) glycyl] benzamide of the formula with 1- (phenyl) -but-1-en-3- on of the formula is reacted in a reducing manner and optionally in a manner known per se the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- [methyl] -3" - [phenyl ] propylamino) ethyl] benzamide of the formula I is converted into an acid addition salt. The invention also relates to the new 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- [phenyl] -but-1" - en-3 "- ylidenimino) ) ethyl] benzamide of the formula V and a process for its preparation. The advantage of these processes is that they can be carried out simply and with high yields and using starting materials which are also readily available in large quantities.

Description

The invention relates to a new process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide and its acid addition salts as well as 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 ", which is a new intermediate product) -yliden-imino) -äthyl] -benzamide and a process for the preparation of the latter.

2- [Hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide is a valuable and widely used small one Alpha and small beta blocking antihypertensive agent.

The prior art discloses several processes for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) - ethyl] benzamide known.

Thus, according to DOS 2 032 642, 2- (hydroxy) -5- (acetyl) -benzamide is brominated, the resulting [small omega (bromine) acetyl] derivative 2- [hydroxy] -5- [2'- (bromo) acetyl] benzamide is combined with N- [benzyl] -N- [1- (methyl) -3- (phenyl) -propyl] -amine or N- [1- (methyl) -3- (phenyl) -propyl] -amine reacted and the resulting 2- [hydroxy] -5- [2- {N- (benzyl) -N- (1- <methyl> -3- <phenyl> -propyl) -amino} -acetyl] -benzamide or 5- [2- {N- (benzyl) -N- (1- <methyl> -3- <phenyl> -propyl) -amino} -acetyl] -benzamide is catalytically hydrogenated, whereby the keto group is reduced and if necessary present N- (benzyl) -protecting group is split off. This method has several disadvantages. The end product is 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide in many process stages only obtained in low yield. That as a starting material N- [Benzyl] -N- [1- (methyl) -3- (phenyl) -propyl] -amine or N- [1- (methyl) -3- (phenyl) -propyl] -amine can also only be used in multiple stages can be produced in a complicated manner.

According to another method described in DOS 2 032 642, 2- [hydroxy] -5- [2 '- (bromo) -acety] -benzamide is reacted with N, N-di- (benzyl) amine and the 2- [Hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamide of the formula IV

brought to implementation with 1- (phenyl) -butan-3-one under reductive conditions. The yields obtained are only mediocre. Another disadvantage of this process is that the 1- (phenyl) -butan-3-one used as starting material is not accessible on a large scale; in fact, there is no description in the literature of any process for producing this compound that is economical even in operation.

In DOS 2 032 642 there is another process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino ) ethyl] benzamide, after which 5- [2 '- (amino) -1' - (hydroxy) ethyl] salicylamide, the means 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) -ethyl] -benzamide, with 1- (phenyl) -butan-3-one, under reductive conditions, for example in ethanol as Medium, reacted or else first reacted with 1- (phenyl) -butan-3-one and the product obtained is reduced, described. In the example, the production of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide is concerned no yield given. The disadvantage of this process lies in the use of 1-phenylbutane-3-one, which is not available on a large scale (see above).

Belgian patent 840 779 and DOS 2 616 403 describe the preparation of the diastereomers of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide by separation of racemic 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl } -propylamino) -äthyl] -benzamide described. According to these processes, as a result of the formation of the chiral center, the number of process steps is increased and the overall yield of the synthesis is decreased.

According to the general formulas given in Hungarian patent specification 165 291, 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) Ethyl] benzamide by condensing 2- [hydroxy] -5- [glyoxyloyl] benzamides and 1- (phenyl) -3- (butyl) amine and subsequent catalytic hydrogenation of the Schiff's base formed. However, this publication does not contain an example of the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide.

The invention is based on the object, while eliminating the disadvantages of the prior art, a process by which the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3 '' - {phenyl} -propylamino) -äthyl] -benzamide in high yields, can be produced in a manner that is easy to carry out even on an industrial scale and using readily available starting materials, as well as creating a new intermediate product for its implementation and a process for its production.

The above has surprisingly been achieved by the invention.

It was surprisingly found that the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] - benzamide from the readily available 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) - ethyl] benzamide of the formula V

can be produced easily and in high yields on an industrial scale.

The invention therefore relates to a process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl ] benzamide of the formula

I.

and of its acid addition salts, which is characterized in that

a) 2- [Hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidene-imino) -ethyl] - benzamide of the formula V is reduced or

b) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} amino) ethyl] benzamide of the formula VI

or 2- [hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamide of the formula IV

with 1- (phenyl) -but-1-en-3-one of the formula

III

is implemented in a reducing manner

and optionally in a manner known per se the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl obtained in this way ] benzamide of the formula I is converted into an acid addition salt.

The hydrogenation of the Schiff base 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) -äthyl] -benzamide of the formula V [variant a)] or the reducing reaction of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} -amino) -äthyl] -benzamides of the formula VI or of 2- [hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamides of the formula IV with the 1- (phenyl) -but-1-en- 3-one of the formula III [variant b)] can be carried out by catalytic hydrogenation. According to an advantageous embodiment of the process according to the invention mentioned, the reduction [variant a)] or reducing reaction [variant b)] is therefore carried out as hydrogenation in the presence of 1 or more catalyst (s). Palladium, platinum or nickel, or a mixture thereof, is or are preferably used for the hydrogenation as catalyst (s). Another example of advantageously usable or concomitantly usable catalysts are Adams catalysts. The catalyst (s) can also be applied to a carrier, for example carbon and / or barium sulfate.

The reducing [variant a)] or reducing reaction [variant b)] can advantageously be carried out in the presence of 1 or more inert organic solvent (s). Preferably, 1 or more ethers, for example diethyl ether, dioxane and / or tetrahydrofuran and / or alcohol (s), for example methanol and / or ethanol, are used as solvents. Tetrahydrofuran is particularly preferably used here. The reduction [variant a)] or reducing reaction [variant b)] can also be carried out in the presence of a small amount of an organic acid, for example glacial acetic acid.

The reduction of variant a) of the process according to the invention is expedient at temperatures of 10 to 40 ° C., in particular 20 to 30 ° C., and under pressures of 0.1 to 1 MPa [1 to 10 atm], in particular 0.2 to 0 , 4 MPa [2 to 4 atm]. It is very particularly preferred to work at 25 ° C. under a pressure of 0.3 MPa [3 atm].

During hydrogenation, 2 equivalents of hydrogen are taken up and both the azomethine bond and the carbon / carbon double bond are saturated.

The yield obtained is almost theoretical.

The reducing implementation of variant b) of the process according to the invention with heating, preferably at temperatures of 50 to 70 ° C. and under pressures of 0.1 to 10 MPa [1 to 100 atm], in particular 4 to 6 MPa [40 to 60], is expedient Atm], especially 5 MPa [50 atm].

The reaction mixture can be worked up in a manner known per se. The end product 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide can be filtered off, for example of the catalyst and evaporation of the filtrate are isolated. The hydrochloride can be isolated in such a way that anhydrous ethanolic hydrogen chloride or a mixture of concentrated hydrochloric acid and ethanol is added to the filtrate.

The 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidene- used in the process according to the invention mentioned as starting material imino) ethyl] benzamide of the formula V is a new intermediate.

The invention therefore also relates to 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidenimino) ethyl] benzamide of the formula V.

The invention also relates to a process for the preparation of this 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) -ethyl] -benzamides, which is characterized in that 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide of the formula

II

or an acid addition salt thereof with 1- (phenyl) -but-1-en-3-one of the formula III

is implemented.

Also the reaction of the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) -ethyl] -benzamide with the 1- (phenyl) -but-1-en-3-one of this latter The process according to the invention can advantageously be carried out in 1 or more inert organic solvent (s). Preferably, 1 or more ethers, for example diethyl ether, dioxane and / or tetrahydrofuran, alcohol (s), for example methanol and / or ethanol, and / or aromatic hydrocarbon (s), for example benzene, are used as solvents Toluene and / or xylene is used. Tetrahydrofuran is again particularly preferably used.

The reaction of the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide with the 1- (phenyl) but-1-en-3-one of the latter according to the invention

The process can advantageously be carried out at temperatures of 25 to 100.degree. C., in particular about 40.degree. If appropriate, it is possible to work in the presence of bases, for example triethylamine or morpholine. This is particularly advantageous if an acid addition salt of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide is used as the starting substance.

The compound obtained 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidene-imino) -ethyl] Benzamide of the formula V can either be isolated or, without isolation, in situ to give 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} - propylamino) ethyl] benzamide of the formula I is reduced, in particular catalytically hydrogenated.

The 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide of the general formula II which serves as the starting substance is expediently one which is obtained by catalytic hydrogenation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} amino) ethyl] benzamide of the formula VI or 2- [hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamide of the formula IV

has been obtained, optionally in situ, used. In this regard, the same expedient, advantageous, preferred and particularly preferred measures apply which were specified above in relation to variant b) of the method according to the invention discussed first.

The main advantages of variant a) of the first process according to the invention are that the compound 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 '' - {phenyl} -but- 1 "- en-3" - yliden-imino) -ethyl] -benzamide of the formula V can be prepared from readily available sources {1- (phenyl) -but-1-en-3-one [benzalacetone]} and the process can also be carried out easily and with high yields on an industrial scale, which also applies to variant b) of the former process according to the invention and the latter process according to the invention.

Without being limited to theoretical considerations, according to our own findings, the former is likely to be attributed to the fact that the keto group of the 1- (phenyl) -but-1-en-3-3 used as starting substance in variant b) of the former process according to the invention in the latter process according to the invention ones [benzalacetones] of the formula III is more reactive than the keto group of the 1- (phenyl) -butane-3-one used according to DOS 2 032 642 as a result of the conjugation. Accordingly, the 1- (phenyl) -but-1-en-3-one of the formula III reacts with the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide of formula II much easier to 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) -äthyl] -benzamide of the formula V, as the intermediate products of DOS 2 032 642, that is 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 '' - {phenyl} -but- 3 "- yliden-imino) -ethyl] -benzamide or 2- [hydroxy] -5- [1 '- (oxo) -2' - (1" - {phenyl} -but-3 "- yliden- imino) ethyl] benzamide.

The invention is explained in more detail with reference to the following examples.

example 1

Production of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) -ethyl] - benzamide

2.30 g (10 millimoles) of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide hydrochloride and 1.46 g (10 millimoles) of 1- (phenyl ) -but-1-en-3-one mixed with 10 ml of tetrahydrofuran, after which the reaction mixture with further stirring or shaking and ice-cooling at a temperature of 10 to 15 ° C 1.20 ml of triethylamine were added dropwise. After the addition was complete, stirring or shaking was continued at room temperature for 5 hours. The precipitated triethylamine hydrochloride was filtered off and the desired product was isolated from the filtrate by chromatography on a silica gel column. Thus 1.56 g (48% of theory) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) ethyl] benzamide with a melting point of 142 to 146 ° C was obtained.

Example 2

Production of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- yliden-imino) -ethyl] - benzamide

2.30 g (10 millimoles) of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide hydrochloride and 1.46 g (10 millimoles) of 1- (phenyl ) -but-1-en-3-one mixed with 10 ml of tetrahydrofuran, after which 4 ml of morpholine were added dropwise to the reaction mixture with further stirring or shaking and ice-cooling at a temperature of 10 to 15 ° C. The reaction mixture was stirred or shaken for 5 hours at room temperature, the precipitated morpholine hydrochloride was filtered off and the filtrate was heated to the boil for 3 hours. The desired product was isolated from the filtrate by chromatography on a silica gel column. So were 2.05 g (63% of theory) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 ' '-yliden-imino) -äthyl] -benzamide with a melting point of 142 to 145 ° C was obtained.

Example 3

Preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide hydrochloride

3.24 g (10 millimoles) of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidenemino) ethyl] benzamide, which has been prepared as described in Example 1 or 2, dissolved in 25 ml of tetrahydrofuran, whereupon 0.5 g of a 10% by weight palladium / carbon catalyst was added and that Mixture was hydrogenated at a temperature of 25 ° C under a pressure of 0.3 MPa [3 atm]. After the end of the reduction, the catalyst was filtered off and 5 ml of ethanol containing 20% by weight of hydrogen chloride were added to the filtrate. The separated white crystals were filtered off and washed with ethanol. Thus 3.46 g (95% of theory) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) ethyl] benzamide hydrochloride with a melting point of 188 to 189 ° C.

Example 4

Preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide hydrochloride

There were a solution of 3.74 g (10.0 millimoles) of 2- [hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamide and 1.46 g (10.0 millimoles) 1- (Phenyl) -but-1-en-3-one in 50 ml of methanol, 1.0 ml of glacial acetic acid, 1.0 g of a 10% by weight palladium / carbon catalyst and 0.1 g of a platinum oxide Catalyst

(after Adams) admitted. The mixture was hydrogenated at 60 ° C under a pressure of 5 MPa [50 atm]. The catalyst was filtered off and the filtrate was concentrated to a small volume. 3 ml of n-propanol saturated with hydrogen chloride and 5 ml of ethyl acetate were added to the residue. The mixture was left to stand, and the precipitated crystals were filtered off and washed. So 2.62 g (72% of theory) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) ethyl] benzamide hydrochloride with a melting point of 187 to 190 ° C.

Example 5

Preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide hydrochloride

A solution of 3.76 g (10.0 millimoles) of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} -amino) -ethyl ] benzamide and 1.46 g (10.0 millimoles) 1- (phenyl) -but-1-en-3-one in 50 ml of methanol, 1.0 ml of glacial acetic acid, 1.0 g of a 10% by weight - igen palladium / carbon catalyst and 0.1 g of a platinum oxide catalyst (according to Adams) were added. The mixture was hydrogenated at 60 ° C under a pressure of 5 MPa [50 atm]. The reaction mixture was worked up in the manner described in Example 4. Thus, 2.77 g (76% of theory) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) ethyl] benzamide hydrochloride with a melting point of 188 to 189 ° C.

Claims (12)

1.) Process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl] -benzamide the formula I. and of its acid addition salts, characterized in that one a) 2- [Hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidene-imino) -ethyl] - benzamide of the formula V reduced or b) 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} amino) ethyl] benzamide of the formula VI or 2- [hydroxy] -5- [N, N-di- (benzyl) -glycyl] -benzamide of the formula IV with 1- (phenyl) -but-1-en-3-one of the formula III implemented reducing and optionally in a manner known per se the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {methyl} -3" - {phenyl} -propylamino) -ethyl obtained in this way ] -benzamide of the formula I converted into an acid addition salt. 2.) Process according to claim 1, characterized in that the reducing or reducing reaction is carried out as hydrogenation in the presence of 1 or more catalyst (s). 3.) Process according to claim 1 or 2, characterized in that the hydrogenation is used as catalyst (s) Palladium, platinum or nickel, or a mixture thereof, is used. 4.) Process according to claim 1 to 3, characterized in that the reducing or reducing reaction is carried out in the presence of 1 or more inert organic solvent (s). 5.) Process according to claim 1 to 4, characterized in that the solvent used is 1 or more ether and / or alcohol (s). 6.) Process according to claim 1 a) or 2 to 5, characterized in that the reduction is carried out at temperatures of 10 to 40 ° C, in particular 20 to 30 ° C, and under pressures of 0.1 to 1 MPa, in particular 0 , 2 to 0.4 MPa. 7.) Process according to claim 1 b) or 2 to 5, characterized in that the reducing reaction is carried out at temperatures of 50 to 70 ° C and under pressures of 0.1 to 10 MPa, in particular 4 to 6 MPa. 8.) 2- [Hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidene-imino) -ethyl] -benzamide of the formula V. 9.) Process for the preparation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (1 "- {phenyl} -but-1" - en-3 "- ylidenimino ) ethyl] benzamide according to claim 8, characterized in that 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide of the formula II or an acid addition salt thereof with 1- (phenyl) -but-1-en-3-one of the formula III implements. 10.) The method according to claim 9, characterized in that the reaction of the 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide with the 1- (phenyl) -but-1-en-3-one in 1 or more inert organic solvent (s). 11.) Process according to claim 9 or 10, characterized in that the solvent used is 1 or more ether, alcohol (s) and / or aromatic [s] solvents. 12.) The method according to claim 9 to 11, characterized in that serving as the starting substance 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (amino) ethyl] benzamide of the general formula II those obtained by catalytic hydrogenation of 2- [hydroxy] -5- [1 '- (hydroxy) -2' - (N, N-di- {benzyl} -amino) ethyl] benzamide of the formula VI or 2- [hydroxy] -5- [N, N-di (benzyl) -glycyl] -benzamide of the formula IV has been obtained, optionally in situ, used.