DE1420955B - alpha- (o-Benzylphenoxy) -beta-piperidinopropane, its acid addition salts and processes for the preparation of these compounds - Google Patents

Description

It has been found that «- (o-Benzylphenoxy) - / J-piperidinopropane of formula I.

C _n H. - CH., -

0-CHo-CH-CH ₃

(D

and its acid addition salts have a much stronger antitussive effect than codeine without significant undesirable effects Have side effects and are therefore valuable medicines for coughing.

The invention accordingly relates to a- (o-benzylphenoxy) - / 3-piperidinopropane, its acid addition salts and a process for the preparation of these compounds by methods known per se.

So you can

a) a L \ - (o-benzylphenoxy) - / 5-propane derivative of general formula Jl

O-CH., -CH-CH ₁

C ₀ H ₅ - CH ₂ -

(Π)

in which Z denotes a halogen atom, a sulfuric acid or sulfonic acid radical, react with piperidine or a piperidyl alkali metal or
b) an o-benzyl phenolate of the general formula III

OX

₅ CH2 ""

(III)

in which X is an alkali metal atom, preferably a sodium atom, with a piperidine compound of the general formula IV

H N-CH ₂ -CH-CH,

(IV)

in the Z has the above meaning to implement, whereby in the latter case as a result of a rearrangement next to the a- (o-Benzylphenoxy) - /? - piperidinopropane the isomer / 3- (o-Benzylphenoxy) -a-piperidinopropane is obtained, which is removed from the reaction mixture. Furthermore, one can

c) o-Benzylphenoxyacetone with N-formylpiperidine implement. One can also

d) «- (o-Benzylphenoxy) - /? - aminopropane with a 1,5-dihalopentane, preferably 1,5-dibromopentane, directly to a- (o-benzylphenoxy) - /? - piperidinopropane implement, or

e) convert a- (o-Benzylphenoxy) - /? - aminopropane with glutaric anhydride to a- (o-benzylphenoxy) - /? - monoglutaramidopropane, convert this with thionyl chloride into «- (o-benzylphenoxy) - /? - glutarimidopropane and the latter finally reduce with LiAlH ₁ to c \ - (o-Benzylphcnoxy) - /? - piperidinopropane. Finally you can

f) the keto group of o - (/ 3-piperidinopropoxy) benzophynons or

g) the hydroxy group of o- (j5-piperidinopropoxy) benzhydrol reduce to the methylene group, with z. B. the reduction in the former case as Wolff-Kishner reduction can be carried out, while the 5 o - (/? - Piperidinopropoxy) benzhydrol z. B. by treatment with a mixture of lithium aluminum hydride and aluminum chloride or by catalytic Hydrogenation in a- (o-benzylphenoxy) - /? - piperidinopropane can be converted.

ίο The one obtained after one of these process variants If appropriate, the free base is then converted into an acid addition salt.

The basic α- (o-benzylphenoxy) - / J-piperidinopropane Forms well-defined acid addition salts with the inorganic or organic acids customary in pharmacy and is more harmless as a medicament, preferably in the form of acid addition salts Acids, e.g. B. hydrochloric acid, sulfuric acid, phosphoric acid, acetic acid, citric acid, tannic acid, 2,6-di-tert-butyl-naphthalene-1,7-disulfonic acid or 2,3-dihydroxy-4,4'-methylene-di-napthoic acid- (2) is used. The salts with the last three acids are poorly soluble and are therefore particularly suitable for the preparation of a suspension that is used as a cough syrup should be, while the easily soluble phosphate is characterized by the fact that it is durable and not is hygroscopic and therefore preferred for the manufacture of an antitussive drug in the Form of z. B. tablets, pills or capsules is used.

The following examples explain the preparation of α- (o-benzylphenoxy) - / 3-piperidinopropane and its Acid addition salts.

example 1

A mixture of 364 g of a- (o-benzylphenoxy) -propyl / Sp-toulolsulfonsäureester and 312.5 g of piperidine was heated under stirring and reflux for 6 hours at 13O ⁰ C, after which the solidified upon cooling reaction mixture was added 500 ml of methanol and the unused piperidine was distilled off together with the added methanol in vacuo. A mixture of the distillation residue with 900 ml of 30% strength aqueous sodium hydroxide solution was

shaken after cooling with ether and then filtered, and the filter residue was washed with ether, 3 times 50 ml, washed. The aqueous phase of the filtrate separated from the ether solution was mixed with 500 ml of ether shaken out, and from the combined ethereal solution

the ether was distilled off after drying with magnesium sulfate, whereupon the distillation residue, 300 g, im Vacuum was distilled. At 164 to 167 ° C / 0.25 mm Hg, 262 g of a- (o-benzylphenoxy) - /? - piperidinopropane distilled.

To a slurry of 100 g of the α- (o-benzylphenoxy) - / 3-piperidinopropane obtained in 100 ml of water was added 323 ml of 1 molar aqueous phosphoric acid solution with water cooling, and the clear solution formed was evaporated in vacuo, finally three times with methanol and once with ether. The white crystalline residue, 144 g, was dissolved in 225 ml of boiling absolute ethanol and filtered off with suction the precipitated from the filtrate of the solution at -20 ⁰ C the reaction product was washed with ethanol and dried in vacuo over sulfuric acid. The yield was 114 g of a- (o-benzylphenoxy) - /? - piperidinopropane trihydrogen phosphate with a melting point of 147 to 149 ° C. After another

3 4

Crystallization from ethanol! Ag the melting point from a filtered solution of the residue in 40 ml of ^{ethanol boiling at 149 to 151 °} C. crystals were precipitated

The “- (o-benzyl suctioned off, twice with ethanol and twice with phenoxy) - /? - piperidinopropane hydrochloride, prepared in an analogous manner, melted, washed with water, dried in the air and then ^{closed at 167 to 169 °} C. 5 at 70 ^° C dried further in vacuo over sulfuric acid B ice η ie 1 2. 14 g of Ä- (o-benzylphene

oxy) - β - piperidinopropane - trihydrogen phosphate with

149.5, mp to 151 ⁰ C - A mixture of 26,1g a- (o-benzylphenoxy). / S-chloropropane and 17 g of piperidine was 32 hours. .

long under reflux until an almost completely io B e ι s ρ ι e 1 4 is formed

solidified reaction mixture at 117 to 134 ⁰ C by adding a solution of 7.7 g of sodium

hitzt, which is then heated for 48 hours in 400 ml of methanol to a solution of 61.4 g o-benzoic to 16O ⁰ C and was then dissolved in methanol. The mixture obtained by zylphenol in 100 ml of methanol, evaporation of the solution in vacuo, was obtained in vacuo with three times the addition of each was treated with 200 ml of 3N hydrochloric acid, and the 100 ml of toluene was evaporated. The residue was dissolved in the resulting oil-water mixture with ether, 3 times 200 ml of hot toluene, whereupon the 100 ml under reflux, shaken out, whereby the water phase boiling clear solution became 396 ml in the course of 5 minutes. The ether phase was washed with water, 3 times 50 ml, a solution of 53.9 g of l-pipsridino-2-chloropropane, and the mixture of the washing water and in toluene was added and the mixture for 10 hours the water phase was evaporated in vacuo, 20 under Was heated to reflux. After cooling, it was finally washed three times with methanol. The resulting un- the reaction mixture initially with 400 ml and then pure hydrochloride, 41 g, was shaken in 100 ml of water with 100 ml of water and the separated dissolved, and that by adding 100 ml of 30% toluene phase initially with 200 ml and then shaken with 103 ml of aqueous sodium hydroxide solution of 3N hydrochloric acid, an oil in which was extracted three times with ether, first with 100 ml of 25 acidic aqueous phase, which after separation and then twice with 50 ml each, whereupon the ether tion of the toluene phase with ether, 2 times 203 ml, extract with water, 4 times 50 ml, washed, shaken with. The oil which had separated out was dried on magnesium sulphate and dissolved in vacuo, and the clear, brown, aqueous phase was evaporated. The fraction which distills during the distillation of the residue after separation from the ether phase in vacuo, 25.2 g, in an oil pump vacuum at 159 to 30 with the three addition of methanol to form a 161 ° C./0.2 mm Hg fraction, 23.2 g , viscous residue, 121.5 g, evaporated, the 703 ml was dissolved in 75 ml of 1 molar aqueous phosphoric acid and dissolved with 400 ml of 30% aqueous, and the solution was evaporated in vacuo, sodium hydroxide solution was added. The result was three times with methanol in the end. The residue, the precipitated base was extracted with ether, 3 times 200 ml, 31 g, was first extracted from 85 ml and then from 80 ml 35 and the ether solution was recrystallized with water, 3 times anolute ethanol and washed for 4 hours 100 ml, dried with magnesium sulfate evaporated at 70 ° C over sulfuric acid in an oil pump and in vacuo. The residue was vacuum dried. The yield was 27 g <x- (o-Ben- distilled twice in vacuo. The fraction boiling at 145.5 bis zylphenoxy) - / S - piperidinopropane trihydrogen phosphate 147 ° C. / 0.15 to 0.03 mm Hg , 81.4 g, with a melting point of 150 to 152 ° C. 40 contained according to a gas chromatographic sub

search 54.7% a- (o-benzylphenoxy) - / J-piperidinopro-

Example 3 _{pan unc} j 45,30 ^ ß- ( _O -Benzylphenoxy) - /? - piperidino-

One on an oil bath with a temperature of propane. A solution of 72.8 g of the isomer mixture 18O ⁰ C heated mixture of 24 g of o-Benzylphenoxy- in 243 ml 0,967molarer phosphoric acid was in Vaaceton and 28.3 g of N-formylpiperidine was over 45 uum three times under addition of methanol eingevon 12 Hours 16.2 g of 85% formic acid evaporated, and the residue, which was slowly distilled off with formic acid by distillation, was added to the mixture, and water was added, and the reaction mixture, after cooling at -20 ⁰ C precipitated crystals then on the oil bath for 12 hours with a line product, 44.2 g, was filtered off, ^{washed with ether ge bath temperature of 180 0} C and then for 2 hours at 5 °, dried in the air and in 140 ml of a bath temperature of Heated to 200 ° C. The reaction boiling ethanol dissolved. The warm solution was mixture was evaporated under vacuum at 200 ⁰ C and filtered and the crystallizes out from the cooled filtrate and catalyzed by the addition of 100 ml of 3N hydrochloric acid for 2 hours Product sulfuric acid heated dried and three under reflux and then cooled and with times from absolute ethanol recrystallized. Ether, 100 ml times and 50 ml twice, were extracted. The 55 32.8 g of pure a- (o-benzylphenoxy) - / S-pip3ridinopropanvereinigte ether extract was washed with ice-cold water, trihydrogenphosphat with melting point 148.8 to 3 times 20 ml, washed, and the obtained hydrochloric acid aqueous 150 ⁰ C. By decomposing 10 g of the phos extraction residue, the phosphoric acid salt was combined with the washing water with aqueous sodium hydroxide and evaporated in vacuo. A solution of the reprocessing and the usual work-up could 5.9 g «- (o-Benzylstandes in 50 ml of water with 50 ml of 30% ßo phenoxy) - / S-piperidinopropane, boiling point 147 to 149 ° C / 0.08 aqueous sodium hydroxide solution was added, and up to 0.09 mm Hg, the isomeric oil precipitated was not bound with ether, 3 times 100 ml, to be obtained. This was found in the extracted during the process, whereupon the acetone-ethanol mother liquor, washed with water, 3 times 25 ml, recrystallization of the crude phosphate mixture and dried with magnesium sulfate in ether. solution was evaporated in vacuo. A solution 65.

of the residue, 12.2 g, in 39.4 ml of 1 molar aqueous Example 5

Phosphoric acid was in vacuo under three times a mixture of 9.7 g of a- (o-benzylphenoxy) - / S-ami-

Evaporated addition of methanol, and the at -20 ⁰ C nopropane, 9.2 g of 1,5-dibromopentane, 8.5 g of anhydrous

Sodium carbonate and 120 ml of absolute ethanol was refluxed for 24 hours and with 50 ml of water are added, whereupon the clear reaction solution is evaporated in vacuo and the residue is dissolved in 80 ml of water and treated with 80 ml of 30% aqueous sodium hydroxide solution. The eliminated Oil was taken up in 150 ml of ether and the ethereal solution was washed with water, 3 times 20 ml, dried with magnesium sulfate and freed from ether in vacuo. The residue, 11 g, was dissolved in 100 ml of 3N hydrochloric acid, an oil separated out, and then extracted with ether, 3 times 25 ml, after which the clear hydrochloric acid solution is evaporated in vacuo with three addition of methanol would. The impure residue, 11.7 g, was recrystallized twice from ethanol and ether. 8.7 g of pure α- (o-benzylphenoxy) - /? - piperidinopropane hydrochloride were obtained obtained with melting point 153.4 to 154.2 ° C.

Example 6

A mixture of 16.1 g of a- (o-benzylphenoxy) -ß-aminopropane, 7.6 g of glutaric anhydride and 50 ml of dry pyridine was heated for 30 minutes at 100 ⁰ C, whereupon the reaction mixture was evaporated in vacuo and then in 50 ml water and 20.5 ml of a 30 ° / ₀ aqueous sodium hydroxide solution was dissolved. 21 ml of 6N hydrochloric acid were added to the clear solution in an ice bath, as a result of which a viscous oil was separated which solidified at -5 ° C. to form a hard crystal mass. The crystal mass, 21.9 g, which was comminuted in the presence of water and washed repeatedly with water and dried in vacuo over sulfuric acid, consisted of «- (o-Ben-

obtained a- (o-benzylphenoxy) - / 3-glutarimidopropane in 10 ml of dry benzene was added dropwise. The reaction mixture was heated in a nitrogen atmosphere at reflux with constant volume by the addition of ether, whereupon ml also in a nitrogen atmosphere first of 1.87 water, then 1.87 ml of a 15 ° / _o aqueous sodium hydroxide solution and finally 3.47 ml Water were added dropwise. After stirring the cooled reaction mixture for 1 hour, the precipitate was filtered off with suction and washed with ether, 5 times 10 ml. The filtrate was extracted with 3N hydrochloric acid, 2 times 50 ml., And the extract evaporated in vacuo, dissolved in 15 ml of water and 15 ml of 30 ° / ₀ aqueous sodium hydroxide solution. The oil which separated out was taken up in 45 ml of ether and the ethereal solution was washed with 30 ml of water, dried with magnesium sulfate and freed from ether in vacuo. The residue, 3.8 g, was distilled in an oil pump vacuum and the main fraction boiling at 140 to 150 ° C./0.16 to 0.10 mm Hg, 2.83 g, in methanol was admixed with 9.84 ml of 0.967 molar aqueous phosphoric acid . By working up the reaction mixture in the direction indicated in Example 4, and several recrystallizations from ethanol and one recrystallization from chloroform, 1.70 g of a- (o-benzylphenoxy) - / -? Piperidinopropan-trihydrogenphosphatmit melting point 141.2 to 148.3 ⁰ C receive.

Example 7

2 g of a- (o-benzylphenoxy) - /? - piperidinopropane and 6.18 g of hydrazine hydrate were refluxed for about 100 minutes, after which the mixture was homogenized by adding 10 ml of ethanol, then zylphenoxy) - £ '-monoglutaramidopropane with melting 35 heated under reflux for a further 21 hours and then point 90.3 to 92 ⁰ C, which was evaporated after two recrystallizations with multiple addition of methanol in vacuo from ethanol and a further recrystallization from to a viscous syrup, 2.02 g. Chloroform-petroleum ether was 92.4 to 93 ⁰ C. This syrup was pulverized along with 1.0 g

12.8 g of the obtained "- (o-benzylphenoxy) - /? - mono-potassium hydroxide in about 30 minutes at 150 ° C glutaramidopropane and 6.4 g of thionyl chloride were heated for 40 minutes, at this temperature for about 30 minutes.

^{heated to 170 °} C. for about 1 hour, whereupon the dark purple reaction mixture was shaken with 60 ml of water and 60 ml of ether and the volatile phase separated from the ethereal solution was shaken out with ether, 3 times 30 ml, with the addition of magnesium sulfate. The combined ether solution was washed first with 30 ml of 3N hydrochloric acid, then with 30 ml of 3N aqueous sodium hydroxide solution and finally with water, 3 times 3U ml, with the addition of magnesium sulfate. hold and after cooling, add 10 ml of water. The separated oil was taken up in 40 ml of ether and the ether solution washed with water, 4 times 40 ml, extracted with 25 ml of 3N hydrochloric acid. The g in vacuo to repeated addition of methanol to a syrup, 1.94, evaporated hydrochloric acid extract was dissolved in 2 ml of hot ethanol and treated with 20 ml of ether, followed by allowing to stand at -20 ⁰ C crystals of a- (o-benzylphenoxy ) -

After drying the washed ether solution with 50/3 piperidinopropane were excreted. The Made Magnesium Sulphate if the ether was removed in vacuo, it was 1.58 g. distilled and the residue, 10.7 g, in an oil. .

pump vacuum distilled. The one at 191 to 204 ° C / 0.15 Example 8

up to 0.17 mm Hg distilling main fraction, 4.1 g, a filtered solution of 30 g oc- (o-benzylphenoxy) -

was recrystallized from 6.7 ml of boiling ethanol, 55 beta-piperidinopropan and 36.6 g of tannic acid in 900 ml which after drying in vacuo over sulfuric acid-methanol was heitiem in vacuo at 80 to 9O ⁰ C 3.9 GA (-o -BenzyIphcnoxy) - /? - glutarimidopropane
with melting point 90 to 94 ° C were obtained, the
by two recrystallizations from ethanol to 92.4
could be increased to 93.2 ^{C C.} From the forward
and final run of vacuum distillation could through
Recrystallization from ethanol another 0.52 g or
0.44 g of the imidopropane with a melting point of 85.2 to
89 ° C can be isolated.

Evaporated a refluxing suspension of 1.52 g of lithium aluminum in a nitrogen atmosphere. The residue was triturated with ether and evaporated again in vacuo and again triturated with ether, filtered, washed with ether, 3 times 150 ml, and air-dried. There were g «- (o-Benzylphenoxy) - / if-piperidinopropane tannate receive.

Example 9

hydride in 75 ml of dry ether, a solution of 5.85 g of the were stirred over the course of 20 minutes A solution of 8.15 g «- (o-Benzylphenoxy) - / J-piperidinopiOpane trihydrogen phosphate in 25 ml of leiuem water was mixed with a solution of 4.45 g Disodium - (2,6- di-tert-butyl - naphthalene) -1,7 - disul -

fonat added to 25 ml of hot water. The precipitated oil was placed in a refrigerator at -5 ° C for crystallization, and repeatedly washed with water and dried in vacuo over sulfuric acid crystals having melting point 235 to 242 ⁰ C were recrystallized three times from methanol and in an oil pump vacuum over sulfuric acid at 60 ° C. . 5.7 ga (-o-benzylphenoxy) - / S-piperidmopropane ^ o-di-tert-butyl-naphthalene-l ^ -disulfonate with a melting point of 245 to 248 ° C. were obtained.

In an analogous manner, 5.24 g of a- (o-benzylphenoxy) - / 9-piperidinopropane trihydrogen phosphate and 5 g of the monopotassium salt of 3,3'-dihydroxy-4,4'-methylene-di-naphthoic acid- (2) 7.2 g of pure α- (o-benzylphenoxy) - ^ - piperidino-3,3'-dihydroxy-4 , 4'-methylenedi (2) naphthoate receive.

Test report

I. Toxicity Studies

1. Acute toxicity

The intraperitoneal acute toxicity and the oral acute toxicity of a- (o-benzylphenoxy) - / 3-piperidinopropane trihydrogen phosphate was determined on albino mice according to Kärber (Arch. exp. Pathol. Pharmakol. 162 [1931], 480).

LD 50 (intraperitoneal administration) 192 mg / kg (corresponding to 146 mg / kg of the free base).

LD 50 (oral administration) 1365 mg / kg (equivalent to 1040 mg / kg of the free base).

For the Ä- (o-Benzylphenoxy) - /? - piperidinopropantannate the following LD 50 values were obtained, the dose being given as the free base.

LD 50 (intraperitoneal administration) 240 mg / kg; LD 50 (oral administration) 1200 mg / kg.

2. Subacute toxicity

Groups of 5 albino rats were fed diets containing 24, 75 and 150 mg, respectively, for 83 days <x> (o-Benzylphenoxy) - /? - piperidinopropane trihydrogen phosphate per kg and day. A group of 5 rats that had the same diet but without the Active ingredient received, served as a comparison. The compound had no effect on food intake and animal behavior. The weight achieved obviously decreased with increasing doses, the difference however, was not statistically significant. At the dissection showed the larynx, thyroid, parathyroid, Heart muscle, lungs, liver, spleen, adrenal gland, kidney and bone marrow no macroscopic or microscopic abnormalities that could be attributed to the active substance. The blood cells were normal in appearance and number.

II. Cough relieving effect in dogs

The antitussive effect of <% - (o-benzylphenoxy) - β - piperidinopropane trihydrogen phosphate after intravenous, oral and intraperitoneal administration was investigated in dogs anesthetized with chloralose. 49 dogs were examined. Three different methods of provoking a cough were used. One was not through breathing (stimulation of the chemo-receptors in the carotid body through lobeline "lobelin cough"), while the other two were through breathing (electrical stimulation of the mucous membrane at the bifurcation of the trachea ("tracheo-bronchial cough" and electrical stimulation of the visceral pleural leaf "pleural cough") were stimulated.

a) Intravenous administration

0.5 mg / kg (4 dogs) showed little or no antitussive effect in the three procedures.

1 mg / kg (12 dogs) led to a complete suppression of the "tracheo-bronchial" and the

ίο »Pleural cough«. The effect came to its fullest Extent immediately after injection and lasted approximately 1 hour. At this dose was the one examined Connection with almost no effect on the "lobelin cough".

2 mg / kg (5 dogs) gave the same effect as

1 mg / kg, but a considerable effect against the "lobelin cough" was also observed.

b) Oral administration

0.5 mg / kg (3 dogs) showed no antitussive effect in any of the three methods.

1 mg / kg (10 dogs) completely suppressed the "tracheo-bronchial cough" and the "pleural cough". The onset of action was slower than after intravenous administration. Compared to the through No effect was observed on lobeline-induced cough.

2 mg / kg (4 dogs) completely suppressed all three types of cough.

c) Comparison with codeine

The antitussive effect of the tested compound was compared with that of codeine. Experiments with dogs given codeine (in the form of the free base) showed that

2 mg / kg were necessary to suppress "tracheo-bronchial" and "tracheal cough". This means, that the tested compound is twice as effective as codeine under the experimental conditions.

III. Clinical examinations

The cough suppressive effect of a- (o-Benzylphenoxy) - /? - piperidinopropane trihydrogen phosphate was tested using tablets containing 15 mg, calculated as the free base, of the compound contained. After a preliminary test, the investigation was carried out in the form of a double blind test, where the compound to be investigated and codeine phosphate (tablets with 30 mg, calculated as free base) and placebos were used. There was also a special objective test to determine the anti-coughing effect in humans »acetylcholine cough test« as described by Haslreiter (Arzneimittelforsch. 9 [1959], 769).

This test was also carried out as a double blind test.

149 inpatients were included in the study (146 men and 3 women in the Ages 34 to 80) who have been ill for 7 to 42 years. 97 patients suffered from chronic Bronchitis or bronchial asthma with bronchitic symptoms. 29 patients had bronchiectasis and 4 silicosis. 18 patients had cough associated with nodular membrane changes Lungs, pleura, or diaphragm, and post-lobectomy conditions.

In the preliminary experiment (24 patients) the dose was fixed (2 tablets 3 times a day). The drug

109 543/389

was well tolerated and did not show any side effects (such as restlessness, dizziness, nausea), who would have required the drug to be discontinued. When examining the blood count, the There were no changes in urine or heart function. The resilience of the bronchi was measured to determine whether administration of the test compound resulted in bronchial relaxation or Respiratory depression leads. The latter was the case when codeine was given. In no case were however, such changes were observed after administration of the compound under study.

The double-blind examinations were carried out in 125 patients. The effect became subjective assessed and described as very good, good or no effect. The following results were obtained:

10

• 5

effect

Very well

Good

No effect

examined
connection

32 ° / o
38%
30%

70%

drug
Codeine

placebo

49%

16%
35%

65%

lO per cent
48%

42%

58%

In the acetylcholine cough test (102 cases), to which an objective rating was applied, received get the following results:

effect

Very well

Good

No effect

examined
connection

40%)
30% 70%
30%)

drug
Codeine

56%)
12% 68%
32%)

placebo

20%)
12% 32% 68%)

These clinical results show that the tested compound according to the invention was found to be antitussive Agent is at least as effective as codeine, but has been found not to has the undesirable side effects of codeine.

35

40

Claims (2)

Patent claims: 1. a- (o-Benzylphenoxy) - / J-piperidinopropane der Formula I. 0-CH ₂ -CH-CH ₃ (I) 5 ° and its acid addition salts. 2. Process for the preparation of the compounds according to claim 1, characterized in that one in a manner known per se a) an α - (0 - benzylphenoxy) - β- propane derivative of the general formula II O-CH ₀ -CH-CH in which Z is a halogen atom, a sulfuric acid or sulfonic acid radical, with piperidine or a piperidyl alkali metal or b) an o-benzyl phenolate of the general
Formula III OX ₅ - CH ₂ - (III) in which X represents an alkali metal atom, with a piperidine compound of the general formula IV H N -CH, -CH-CH, (IV) in which Z has the above meaning, converts or c) 0 - benzylphenoxyacetone reacts with N-formylpiperidine or d) ac - (o-benzylphenoxy) -ß- aminopropane is reacted with a 1,5-dihalopentane or e) ix- (o-Benzylphenoxy) - /? - aminopropane with glutaric anhydride to «- (o-benzylphenoxy) -ß-monoglutaramidopropane, this with thionyl chloride in« - (o-benzylphenoxy) -ß-glutarimidopropane converted and the latter finally with LiAlH ₄ reduced to a- (o-benzylphenoxy) - / S-piperidinopropane or f) the keto group of o - (/? - piperidinopropoxy) benzophenone or g) the hydroxy group of o - (/ 3-piperidinopropoxy) benzhydrol reduced to the methylene group and the free base thus obtained, optionally in a Acid addition salt transferred.