FR2653765A1 - Process for the enantioselective preparation of 2-aminotetralins - Google Patents

Abstract

The invention relates to a process for the enantioselective preparation of 2-aminotetralins of formula (I) in which R represents hydrogen or a lower alkyl group and the asterisk denotes that the carbon atom thus labelled has a specific absolute configuration, and of their acid addition salts, starting from a phenol ether of formula in which R DEG is a lower alkyl group and from the anhydride of optically active N-(trifluoroacetyl)aspartic acid of formula via novel intermediates of formula in which R DEG and the asterisk have the meaning given above and X represents an oxygen atom or two hydrogen atoms.

Description

dans laquelle R représente lthydrogène ou un groupe alkyle inférieur et l'astérisque dénote que Atome de carbone ainsi marqué a une configuration absolue détérminée qui peut être soit la configuration
R soit la configuration S, et de leurs sels d'addition dtacides; et les nouveaux intermédiaires utilisables dans la synthèse de ces produits.The present invention relates to a process for the enantioselective preparation of 2-aminotetralins of formula (I)

wherein R is hydrogen or a lower alkyl group and the asterisk denotes that the carbon atom thus labeled has an absolute configuration determined which may be either the configuration
R is the S configuration, and their acid addition salts; and the new intermediates that can be used in the synthesis of these products.

 In the present description and in the claims which follow, the term "lower alkyl" designates a monovalent radical of a saturated hydrocarbon containing 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl or sec-butyl. methyl radical is particularly preferred.

 The term "tetralin" refers to 1,2,3,4-tetrahydronaphthalene, and the term "tetralone" to the corresponding derivative wherein one of the -CN - groups has been replaced by a -CO- group.

qui ont été décrites dans la demande de brevet européen EP-A-211721.The compounds of formula (I) are useful as intermediates in the preparation of the corresponding phenylethanolaminotetralins of formula (II)

which have been described in European Patent Application EP-A-211721.

 According to this document, the compounds of formula (II) and their pharmaceutically acceptable salts have very interesting pharmacological properties having shown a particularly pronounced lipolytic activity.

 According to the European Patent Application EP-A-211721, the products of formula (II) are prepared according to various procedures which generally comprise the reaction of a substituted 2-aminotetraline with a styrene epoxide, a phenylglyoxal, or an alphahalocetophenone .

 Still according to the above European patent application, the products of formula (II) can be prepared in the form of diastereoisomers or optically pure stereoisomers. However, the objection to optically active stereoisomers generally involves successive crystallizations at the level of the final product which reduce yields and, above all, result in rather laborious operations.

 In the European patent application EP-A-303545 it is stated that by reacting a 2-amino-7-hydroxytetralin with a mandelic acid an amide is obtained in the form of a mixture of racemates which are in a diastereoisomeric relationship with each other. which can be separated and reduced to phenylethanolaminotetralins in the form of racemates without interfering with the stereochemistry of the products.

 Starting from a racemic aminotetralin and an optically active mandelic acid or, vice versa, starting from an optically active aminotetralin and a racemic mandelic acid, an amide is obtained in the form of diastereomers separable by chromatography which, after separation, give, by reduction, the corresponding phenylethanolaminotetralins optically pure.

 According to the European patent application EP-A-303545 the optically active 2-aminotetralins of formula (I, R = -H) are prepared by resolution of the racemate of 7-methoxy-2-aminotetralin according to conventional methods, in particular by salification with an optically active acid, preferably (+) and (-) mandelic acid, followed by the demethylation of the -OCH3 group.

 However, the problems concerning the separation of a racemate by formation of the corresponding diastereoisomeric salt are obvious to any person experienced in chemistry: the yields are low, especially if it is desired to obtain a product having a very high enantiomeric purity, and the The results are not reproducible so that each preparation must be subjected to an analysis specifically developed for the control of enantiomeric purity.

dans laquelle RO est un groupe alkyle inférieur, et de l'anhydride de l'acide N-trifluoroacétyl-aspartique optiquement actif de formule (IY)

dans laquelle l'astérisque a la même signification donnée ci-dessus.It has now been found that it is possible to prepare the compounds of formula (I) in optically pure form by a stereoselective preparation process starting from a phenol ether of formula (III)

wherein RO is lower alkyl, and optically active N-trifluoroacetylaspartic acid anhydride of formula (IY)

in which the asterisk has the same meaning given above.

 Enantioselective syntheses of compounds containing the tetralin moiety are known in the literature.

 European Patent Application EP-A-251547, for example, describes the enantioselective synthesis of (+) trans-la, 2,3,4a, 5,6-hexahydro-9-hydroxy-4-propyl-4H-naphtha - [1,2-b7-1,4-oxazine via 2,3-methyl, 2,3,4-tetrahydro-1-hydroxy-7-methoxy-2-naphthalenyl] carbamic acid methyl ester and JE Norlander et al., J. Org. Chem. 1985, 60, 3619-22, describe the preparation of 2-amino-6,7-dihydroxy-1,2,314-tetrahydronaphthalene.

 However, the starting compounds used in the two known methods are different from those used according to the process of the present invention (in particular in the two known syntheses, the starting material is a phenyl bearing two substituents) and, in addition the reaction conditions provided for in certain steps of said syntheses are not suitable for industrial use of these processes or can not be used for the preparation of the compounds of formula (I).

dans laquelle RO est un groupe alkyle inférieur, avec un anhydride N-trifluoroacétylaspartique optiquement actif de formule (IV)

Thus, according to one of its aspects, the present invention relates to a process for the preparation of the compounds of formula (I) above, characterized in that (a) a phenol ether of formula (III) is treated

wherein RO is a lower alkyl group, with an optically active N-trifluoroacetylaspartic anhydride of formula (IV)

in the presence of a Friedel-Crafts catalyst, (b) the ketone group of the compound thus obtained is reduced by
formula (V)

by catalytic hydrogenation over a palladium catalyst in
an acid medium, Cc> cyclizes the intermediate product of formula (VI)

obtained in (b), in the presence of a chlorinating agent and
of a Friedel-Crafts catalyst, (d) the cyclized product of formula (VII) is subjected

to a catalytic hydrogenation on a palladium catalyst
in an acid medium, and (d ') optionally isolates
minor amounts of the compound of formula (I) wherein R is alkyl
lower R "; (e) subjecting the compound of formula (VIII)

obtained, as the main component, - in step (d) to a
lation, to obtain a compound of formula (I) in which R is
a lower alkyl group, and (f) optionally, if it is desired to obtain a compound of formula (I)
wherein R is hydrogen, the compound of formula
(I) wherein R is a methyl group, obtained as described
above, starting from a compound of formula (III) in which
RO is methylated to demethylation.

the compounds of formula (I) thus obtained may be isolated in the form of free bases or acid addition salts or may be converted therein.

The method of the present invention is better illustrated by the
Diagram A next:
SCHEME A

<tb><SEP> ORa <SEP> O <SEP> ORO
<tb><SEP> 0
<tb> COOH
<tb><SEP> NHCOCF3 <SEP> COCH <SEP> -IH-NHCOCF
<tb><SEP> (III) <SEP> CIV) <SEP>'<SEP> (V)
<tb><SEP> ORO
<tb><SEP> (V) <SEP> (b) <SEP> Eli
<tb><SEP> COOH
<tb><SEP> 2CHaCHNHCOCF3
<tb><SEP> (VI)
<tb><SEP> o
<tb><SEP> F
<tb> CVI) <SEP>. <SEP> W <SEP> X <SEP> OR <SEP>(vrr>
<tb><SEP> (VII)
<tb><SEP> F <SEP> CCHN <SEP> OR0
<tb><SEP> 3 <SEP> It <SEP> *
<tb> (VII)
<tb><SEP> H2N <SEP> ORO
<tb><SEP> I: <SEP> 2 <SEP> ziziR <SEP> = <SEP> lower alkyl <SEP>)
<tb><SEP> I (f)
<tb><SEP> RO <SEP> =
<tb><SEP> H2N <SEP>>"> sY <SEP>" ssY <o <SEP> OH
<tb><SEP> (I: <SEP> 1! <SEP> J <SEP> (I <SEP> R <SEP> = <SEP> H)
<Tb>
The starting compounds of formulas (III) and (IV) are known products.

 In particular, the compounds of formula (III) are commercial products while the two pure enantiomers of formula (IV) can be easily and quantitatively obtained by treatment of the corresponding aspartic acid, L- or D-, with anhydride trifluoroacetic.

 The reactions provided by the process of the present invention do not involve modification of the stereoconfiguration of the carbon atom marked with the asterisk.

 In particular, starting from L-aspartic acid, the S-isomer of the 2-aminotetralins of formula (I) is obtained, whereas starting from D-aspartic acid yields the R-isomer.

 In detail, the Friedel-Crafts reaction provided for in step (a) is carried out, in the presence of a Lewis acid, in a nitrated organic solvent such as nitrone-nitrone or nitrobenzene, optionally mixed with one or more solvents. normally used in Friedel-Crafts acylations such as 1,2-dichloroethane, methylene chloride, disolfide carbon, ethers.

 Preferably, mixtures of nitromethane and 1,2-dichloroethane or mixtures of nitromethane and methylene chloride are used.

 The compound of formula (III), as well as the Lewis acid, are used in amounts at least equimolar relative to the anhydride of formula (IV), but preferably in excess.

 Very satisfactory results have been obtained using Ale13, as Lewis acid, and in particular using amounts of AlCl 3 and the starting ether (III) almost double with respect to the amount of the anhydride. (IV).

 The reaction temperature is, in general, between -50 ° C. and room temperature, preferably between 0 ° C. and 10 ° C.

 At the end of the reaction, the product thus obtained is recovered according to the known procedures, by treatment of the reaction mixture with cold water, separation of the organic phase and extraction with a basic aqueous solution containing, preferably, an alkaline bicarbonate , such as sodium bicarbonate.

 The product (V) is recovered by acidification of the aqueous solution, extraction with an aprotic organic solvent which is not miscible with the aqueous solution and evaporation of the organic solvent.

 According to a preferred aspect of the present invention, the product (V) is directly subjected to reduction of the # C = O group to # CH2 group according to step (b).

 This reduction is advantageously carried out by catalytic hydrogenation on a palladium catalyst, preferably palladium on carbon or asbestos, in an alcoholic solvent in the presence of small amounts of a strong acid, such as sulfuric acid, perchloric acid or p-toluenesulfonic acid.

 The reduction can also be conducted using acetic acid as a reaction solvent. In this case, the addition of another acid can be avoided.

 The catalytic hydrogenation can be conveniently carried out at room temperature, under ordinary pressure or under hydrogen pressure.

 The progress of the reaction can be monitored by evaluating the amount of adsorbed hydrogen.

 When the theoretical amount of hydrogen has been adsorbed, the reaction is terminated, the catalyst is filtered off and the intermediate product is isolated according to standard techniques.

For example, the reaction mixture can be neutralized by using a conventional basic agent, such as an alkaline carbonate or bicarbonate, evaporating the solvent, dissolving the resulting residue in water and precipitating the product by acidification.

 The product thus isolated, which can be further purified by crystallization, is substantially pure and in particular contains no ortho-substituted isomer.

 The cyclization reaction can be carried out, in step (c), in a single step using a chlorinating agent, which converts the carboxylic group to the corresponding acid chloride, and a Lewis acid, which catalyzes the intramolecular cyclization of the intermediate without the latter to be isolated.

 To convert the -COOR group into the -COC1 group, it is possible to use conventional chlorination agents or systems, such as phosphorus chlorides, namely PICS,, PCI5 and POCSI, or thionyl chloride or oxalyl chloride. in the presence of DMF.

 Lewis acids, such as AlCl3, FeCl3, TiCl4 and, preferably, SnCl4, as well as the solvents conventionally used in Friedel-Crafts acylations, such as 1,2-dichloroethane, methylene chloride, nitromethane, nitrobenzene and similar, can be used to perform this cyclization.

 In this case too, it is possible to use at least equimolar amounts with respect to the compound (VI), but preferably in excess, of chlorinating agent and of Lewis acid.

 The reaction is preferably carried out at a temperature between -5 ° C and room temperature, or more preferably between 0 ° C and 10 ° C.

 The product of formula (VII) is recovered according to conventional techniques. For example, the reaction mixture is treated with ice water, the organic phase is separated, the solvent is evaporated and, if desired, the product (VII) is purified by crystallization.

 In step o, the compound (VII) is hydrogenated on a palladium catalyst, in particular palladium on an inert support, for example on charcoal or asbestos, in a strong acid-containing acetic acid medium, such as sulfuric acid, perchloric acid or p-toluenesulfonic acid.

 The reaction may conveniently be carried out at room temperature and ordinary pressure or, alternatively, under hydrogen pressure.

 At the end of the reaction, the catalyst is removed by filtration, the strong acid is neutralized by addition of a base or a buffer, preferably sodium acetate, and the solvent is evaporated. The residue thus obtained is taken up in water and filtered.

 The product remaining on the filter is the compound of formula (VIII), which is separated and used for the next step either directly or after further purification, preferably by washing for example first with water, then with a solution of an alkaline bicarbonate, for example sodium, and finally again with water and by drying.

 The product dissolved in the mother liquor at the end of step (d) is already the compound of formula (I), wherein R is a lower alkyl group RO.

 According to step (d '), in order to recover the latter product, the mother liquors are made basic, they are extracted with an organic solvent and the product of formula (I) is precipitated, where R is a lower alkyl group R ", of the organic phase containing it, by adding an acid giving rise to one of its addition salts.

 If desired, the free base can be liberated by nebutralization and optionally converted into another salt according to known methods.

 The product of formula (VIII) is then deacylated, according to step (e), either in a strongly acidic medium with a mineral acid such as hydrochloric acid, or in an alkaline medium, for example with a hydroxide or an alkaline carbonate, preferably sodium. In the first case, the product of formula (I), where R is a lower alkyl group RO, thus obtained, can be isolated directly in the form of the addition salt by the mineral acid used for the deacylation.

 The two portions of the compound of formula (I), where R is a lower alkyl group RO, obtained at the end of steps (d ') and (e), are combined and, if necessary or advisable, purified by crystallization.

 Finally, the compound of formula (I), in which R represents hydrogen, is easily obtained starting from the compound of formula (I), in which R = RO = methyl, having the same absolute configuration at the atom of asymmetric carbon, by demethylation according to known techniques, in particular by 48% hydrobromic acid.

 The product (VII) and the compound of formula (VIII), obtained as the main product by catalytic hydrogenation of the compound (VII) according to step Cd), are novel products and represent the key intermediates of the process of the present invention. .

dans laquelle RO et l'astérisque ont la même signification que ceLle donnée cidessus et X représente un atome d'oxygène (composé de formule (VII) ci-dessus) ou deux atomes d'hydrogène (composé de formule (VIII) cidessus).Thus, the present invention also relates, in another of its aspects, to a compound of formula

in which RO and the asterisk have the same meaning as above and X represents an oxygen atom (compound of formula (VII) above) or two hydrogen atoms (compound of formula (VIII) above).

The following examples illustrate the invention without however limiting it. The rotational power values are indicated as
20 / alpha /, but we must hear them as Calpha7D
PREPARATION I
N-trifluoroacetyl-L-aspartic anhydride.

To gently stirred trifluoroacetic anhydride (100 ml) was added L-aspartic acid (40 g, 0.3 mol). The mixture is heated at 400.degree. C. for 5 minutes until clear, and then heated under reflux (external temperature of approximately 600.degree. C.) for 25 minutes. After cooling, petroleum ether (about 400 ml) is added. The voluminous precipitate thus obtained is stirred vigorously, filtered and washed with petroleum ether (about 100 ml). The product is dried in a forced ventilation oven to give Ntrifluoroacetyl-L-aspartic anhydride (63.3 g, 100%); m.p. 134-135 C; / alpha / t -38.8 "(methanol, c = 0.5%).

EXAMPLE 1 a) (L) 4- (4-Methoxyphenyl) -4-oxo-2-trifluoroacetamido acid
butanol ((V): R = CH 3 -).

Anhydrous AlCH (28 g, 0.21 moles) is added to a mixture of
dichloroethane (260 mL) and nitromethane (48 mL) cooled to 0-50C,
maintaining the reaction temperature below 7-8 C.

The mixture is stirred cold for 15 minutes and then
add N-trifluoroacetyl-L-aspartic anhydride (22 g, 0.104
mole) and anisole (22.2 g, 0.205 moles) without exceeding 7-8 C.

The reaction mixture is stirred cold for 60 minutes and
room temperature for 2 days and then poured
in a mixture of water (500 ml) and ice (500 g) and shake it
energetically. The product is extracted with chlorine
methylene (3 x 200 ml) and the organic phase is washed with acid
1N hydrochloric acid and then with water. The product is extracted
a solution of sodium bicarbonate 1N C3.x 350 ml), filtered
this aqueous solution on paper and makes it strongly acidic
by hydrochloric acid. The product is extracted with
methylene chloride (3 x 300 ml) and the extracts are washed
combined once with water.It dries on sodium sulphate,
evaporated under vacuum and a residue (29 g, 87Z) is obtained which
is used as is in the next step.

(b) 4- (4-Methoxyphenyl) -2-trifluoroacetamidobutanoic acid (L)
CCVI): R = -CH3).

The compound obtained above (29 g, 0.09 mol) is dissolved in
absolute methanol (180 ml) with gentle heating, add a
concentrated sulfuric acid solution (1.4 ml) in methanol (20 ml)
ml) and finally 10% palladium on charcoal (2.3 g). We submit
hydrogenation reaction mixture at the pressure and the
ambient temperature. After 90 minutes, filter and add to
the solution of sodium carbonate (14.3 g). We evaporate the soil
under vacuum and the residue is taken up with water (500 ml). We
filters the solution thus obtained on paper and makes it acidic
with dilute hydrochloric acid. We filter the product
precipitated and dried by obtaining (L) 4- (4-methoxy)
phenyl) -2-trifluoroacetamidobutanoic acid (18 g, 65%); mp

 108-1150C; / alpha / = +7.80 (methanol, c = 0.5%).

A reprecipitated sample in Liteau (bicarbonate / chloric acid
hydric) melts at 1200C; / alpha / = +8.5 (methanol, c = 0.5%).

The elemental analysis and the IR and NMR absorption spectra are
in accordance with the assigned structure.

c) (L) 7-methoxy-2-trifluoroacetamido-1-tetralone ((VII): R = -CH3).

The compound obtained is dissolved as described in the previous step
(34 g, 0.11 mol) in dichloroethane (830 ml) and cooled
the resulting solution at 0-5 ° C with stirring.
portions, PCk (28 g, 0.13 mole) while maintaining the temperature
below 7-80C. It is stirred cold for 2 hours and then
SnCl.sub.14 (34 ml, 0.29 moles) was added. We keep the mixture
reaction with cold stirring 15 minutes and then 4
hours at room temperature, it is poured into ice (1
kg) while stirring vigorously and separating the two phases.

The aqueous phase is extracted with dichloroethane (250 ml
ron), the two organic extracts are combined and the two
once in the water. After drying of the organic phase on sulphate
of sodium, the organic solvent is evaporated under vacuum and
take the residue with isopropyl ether (60 ml). It is
leave a few hours in the refrigerator, filter and
Wash with a little isopropyl ether. We thus obtain the (L)
7-methoxy-2-trifluoroacetamido-1-tetralone (25.5 g, 80%); mp

160-165 ° C / alpha / = -83.1 (methanol, c = 0.5%) This compound is
used as is in the next step.

A sample of this product is crystallized in isopropanol
using a product / crystallization solvent ratio of
viron 1/7; mp 163-166 ° C; / alpha / = -87.40 (methanol, c =
0.5%).

d) (L) 7-methoxy-2-trifluoroacetamidotetralin ((VIII): RO = -CH).

The compound obtained is dissolved as described in the previous step
(25.5 g, 0.089 mol) in acetic acid (400 ml) under heating
slowly and add a solution of sulfuric acid
concentrate (12 ml) in acetic acid (50 ml) and
palladium on charcoal at 10X (2.6 g) in acetic acid (50
mid). The above product is subjected to a hydrogenation at
ambient pressure and at 25 ° C. After 90 minutes,
filtered, an aqueous solution of sodium acetate is added
trihydrate (68 g in 500 ml) and evaporated to dryness. We take back
the residue is washed with water (500 ml) and ground
The solution to be used for step (d) ci
underneath and wash the product on the filter first with
liteau, then with a saturated solution of sodium bicarbonate
and finally to the water and dried in a drying oven
forced lation. The (L) 7-methoxy-2-trifluoro is thus obtained
acetamidotetralin C14.6 g, 602); mp 113-118 ° C; / alphal = -860
methanol, c = 0.5%).

 d) L (-) 2-amino-7-methoxytetraline hydrochloride.

 ((I): R = R = -CH3).

The separated filtrate is recovered as described above, it is made
strongly basic by ammonium hydroxide solution
concentrated and extracted with ethyl acetate (3 x 100 ml).

After drying over sodium sulfate, evaporate under pressure
reduced, the residue is taken up in isopropanol (20 ml) and
a solution of hydrochloric acid in isopropanol is added.

The L (-) 2-amino hydrochloride is separated by filtration.
7-methoxytetralin precipitated (3.1 g, 15%); mp 200-2030C;
/ alpha / - -65.20 methanol, c = 0.5 :).

e) LC-) 2-Amino-7-methoxytetraline hydrochloride.

L (-) 7-methoxy-2-trifluoroacetamidotetralin (5.5
g, 0.02 mol), obtained as described in step (d) above,
in 95% ethanol (65 ml) and added a solution of
concentrated hydrochloric acid (32.5 ml) in 95% methanol
(30 ml). Refluxed with gentle shaking for 3 hours
and then evaporate dry. The residue is taken twice
acetone and evaporate to dryness. The residue is taken up by
acetone (20 ml) and after about 30 minutes filtered. We ob
thus holds L (-) 2-amino-7-methoxytetra hydrochloride
line (3.2 g). It is crystallized with absolute methanol (32 ml)
and, after one night, one filters. This gives 2.15 g of product
(50Z), mp 203-2050C; / alphal = -66.10 methanol, c = 0.5 2).

f) S (-) 2-amino-7-hydroxytetralin.

The two batches of L (-) 2-amino hydrochloride are pooled
-7-methoxytetralin obtained in steps (d ') and (e) above
(in total 5.1 g, 0.0239 mol), the whole is suspended in acid
48% hydrobromic solution (63 ml) and the mixture is heated to
external temperature of about 130-140 C, for 3 hours under
gentle agitation. The solution obtained is evaporated to dryness, the residue is taken up in ethanol and evaporated to dryness twice. The residue is taken up in water (18-20 ml) and the solution is made strongly basic with a concentrated solution of sodium hydroxide. After one night in the refrigerator, the precipitated product is filtered off and washed with a small amount of water. It is dried in a forced ventilation oven and then heated very slowly to 1000.degree. water of crystallization. There is thus obtained S (-) 2-amino-7-hydroxytetralin as an anhydrous product (3.35 g, 85%); mp 143-145 ° C, alpha = 87.70 (methanol, c = 0.5%).

Another object of the present invention is S (-) 2-amino-7-hydroxytetralin in anhydrous form, which is a novel product.

Starting from a L (-) 2-amino-7-methoxytetraline hydrochloride having a / alpha / -670 (methanol, c = 0.5%), the
L (-) 2-amino-7-hydroxytetralin, as anhydrous product, having a / alpha / = -920 (methanol, c = 0.5 Z).

Claims (10)

 wherein R is a lower alkyl group, with an optically active N-trifluoroacetylaspartic anhydride of formula (IV)

 wherein R is hydrogen or an alkyl group containing 1 to. 4 carbon atoms and the asterisk denotes that the state of the carbon thus marked has an absolute configuration determined, or an acid addition salt thereof characterized in that (a) a phenol ether is treated of formula (III)

Process for the enantioselective preparation of a 2-aminotetralin of formula (I)

 of formula (V)  in the presence of a Friedel-Crafts catalyst, (b) reducing the ketone group of the compound thus obtained

 in an acid medium (c) the intermediate product of formula (VI) is cyclized  by catalytic hydrogenation over a palladium catalyst

 Friedel-Crafts catalyst, (d) subjecting the cyclized product of formula (VII)  obtained in the presence of a chlorinating agent and a

 CI) where R is lower alkyl Ro, (e) subjecting the compound of formula (VIII)  optionally minor amounts of compound of formula  palladium in an acidic medium, and Cd ') is isolated  to a catalytic hydrogenation on a catalyst at  processed.  in the form of free bases or acid addition salts or to be  the compounds of formula (I) thus obtained which can be isolated  formula (III) in which RO is methyl, onemethylation;  obtained as described above, starting from a compound of  compound of formula (I) wherein R is a methyl group  formula (I) in which R is hydrogen, the  Cf) optionally, if it is desired to obtain a compound of  which R is lower alkyl, and  deacylation, to obtain a compound of formula (I) in the  obtained, as the main compound, in step (d) to 2.Procédé according to claim 5 for the enantio preparation  a selective 2-aminotetralin of formula (I) in which R  is hydrogen or a methyl group, characterized in that  from a compound of formula (III) in which RO is methyl. 3.Procédé according to claim 5 for the preparation of a  2-aminotetralin of formula (I) wherein R is hydrogen  or a methyl group and the absolute configuration of the atom of the  asymmetric carbon is the configuration (S), characterized in that  starting from a compound of formula (III) in which RO is  methyl and N-trifluoroacetyl-L-aspartic anhydride. 4.Procédé according to claim 5 characterized in that conduit  the Friedel-Crafts reaction provided in step (a) in a soil  organic nitrate, possibly mixed with one or more  other solvents commonly used in acylations  Friedel-Crafts, in the presence of Ale13 as a catalyst for  Friedel-Crafts. 5.Procédé according to claim 4 characterized in that conduit  the Friedel-Crafts reaction provided for in step (a) in a  mixture of nitromethane and 1,2-dichloroethane. 6.Procédé according to claim 4 characterized in that conduit  the catalytic hydrogenation provided in step (b) in a solvent  alcoholic in the presence of a strong acid selected from acid  sulfuric acid, perchloric acid and p-toluenesulphonic acid,  or in acetic acid.  sulfuric acid, perchloric acid or p-toluenesulfonic acid.  acetic acid in the presence of a strong acid selected from acid  the catalytic hydrogenation provided in step (d) in the acid 7, Process according to claim 4 characterized in that duct

8, Compound of formula  determined.  that the carbon atom thus marked has an absolute configuration  oxygen atom or two hydrogen atoms and the asterisk denotes  wherein RO is a lower alkyl group, X represents a  trifluoroacétamidotétraline.  Compound according to claim 8, which is (S) 7-methoxy-2 The compound of claim 8 which is (S) 7-methoxy-2  trifluoroacetamido-the-oxotétraline.  11.S (-) 2-amino-7-hydroxytetralin anhydrous.