DE1618297C3 - Process for the production of basic ethers - Google Patents

Description

Η —Ζ

in which Z has the above meaning.

2. The method according to claim 1, characterized in that in the first stage benzene, Diethyl or dibutyl ether is used as a solvent.

wherein R is hydrogen, straight or branched alkyl groups having 1 to 12 carbon atoms or a phenyl radical optionally substituted by one or more identical or different halogen atoms, alkyl, trifluoroalkyl, alkoxy and / or alkyl mercapto groups, A a straight or branched lower alkylene radical, Z an amino -, alkylamino or dialkylamino group or a 5- to 8-membered saturated cyclic alkyleneimino group, optionally containing a further heteroatom and optionally substituted by alkyl, alkoxy, hydroxyalkyl, acyl or acyloxyalkyl groups, η for an integer from 3 to 7, m is an integer from 0 to 4, characterized in that a dioxa-spiroalkane of the general formula II

(Π)

wherein A and η have the above meaning with an organic metal compound of the general formula III

R- (CH ₂ ) "rM (III)

where R and m have the above meaning and M stands for an alkali atom or a - Mg-halogen group, expediently in an aromatic hydrocarbon or ether, converts the glycol monoether obtained after decomposition of the resulting complex in weakly acidic or neutral solution general formula IV

(CH ₂ LR

O-A-OH

(IV)

in which A, R, m and η have the above meanings, converted in a manner known per se into a mesyl or tosyl ester and either this directly in a manner known per se with an amine of the general formula V

H-Z

(V)

where Z has the above meaning, reacts or initially carries the mesyl or tosyl ester with it The invention relates to a process for the production of valuable, pharmacologically active basic Ethers.

Pharmacologically active basic ethers of certain cyclic tertiary alcohols have been found in the literature already described. Some basic 1-phenyl-cyclohexyl-ethers have been reported (Chem. Listy, 42, 175, 1948) that they show a weak antihistamine effect. Furthermore, basic ethers were replaced by cyclic ethers tertiary alcohols as agents with anti-Parkinsonism or inhibitory effects on the central nervous system Effect described (DT-PS 10 90 201, 10 94 738, 1090347 and 1110 155). The connections were made mostly from optionally substituted 1-phenyl- or 1-benzyl-cycloalcohols by etherification with basic Group-containing alkyl halides prepared

Our own investigations have further shown (Hungarian patent specification 1 51 865) that the various basic ethers of 1-aryl-, 1-aralkyI- and 1-lower-alkyl-cycloalkanols primarily spasmolytic, tranquilizing, peripheral vasodilatory, local anesthetic and the experimental ulcer inhibitory effects and Parkinsonism not or affect only insignificantly. The preparation of this compound was carried out by the well-known Williamsonsche Ether synthesis and also using reactive esters such. B. the mesyl and tosyl esters.

There were also various basic 1-alkyl cycloalkanol ethers prepared and found that these compounds have the aforementioned pharmacological Properties essentially also have, but that some of the compounds are characteristic Have properties as so-called minor tranquillizers.

The processes known heretofore for the preparation of these compounds have various significant ones Disadvantage. Some of the desired compounds cannot be found with the help of Williamson's ether synthesis or isomerization can occur under the action of basic condensing agents. In some cases the yields are also unsatisfactory and produced in this way Products are very difficult to clean.

The production of such basic ethers by reacting l-benzylcycloalkanol with basic substituted alkyl halides or with the corresponding

chenden haloalkanols and the implementation of these compounds to the corresponding salts and quaternary ammonium compounds were already known (DT-AS 10 94 738).

It has also already been proposed to implement a cycloalkanone with a Grignard compound, the To decompose formed complex and the resulting cycloalkanol with a basic alkyl halide to be implemented (DT-OS 14 33 813).

It has also been proposed to react the corresponding cycloalkanols or their alkafimetallic derivatives with substituted alkyl halides or by reacting reactive esters of cycloalkanols with substituted alkanols to produce similar ether halides (DT-OS 15 68 462).

On the other hand, it was known (Tschoubar and Verr i e r, Bull. Soc. Chim. France 1960, 2151-2156) that the reaction of alkyl halides with the corresponding alcoholates even takes 18 hours Cooking in toluene can only achieve a 15% conversion; instead of substitution takes place almost an elimination reaction takes place completely. If you try, for example, under the reaction conditions of DT-AS 10 94 738 to produce the corresponding glycol half-ether starting from the alcoholate, so occurs does not get the desired response. When implementing the tertiary benzyl-substituted cycloalkanol with Compounds of the formula

Cl- (CH ₂ J ₃ -R,

where R is chlorine, OH or -N (Ch ₃ J ₂ , 93.5% of the starting compound is recovered in unchanged form.

The invention is therefore based on the object, proceeding from the easily derived from the corresponding Cycloalkanone obtainable dioxaspiroalkane a process for the production of basic ethers or their salts or to make quaternary ammonium compounds accessible, in which good in every process stage Yields can be achieved.

The invention therefore relates to a process for the preparation of basic ethers of the general types Formula I.

(CH ₂ ) -R organic metal compound of the general formula III

(CH ₂

(D

Ο — Α —Ζ

40

45

wherein R is hydrogen, straight or branched alkyl groups having 1 to 12 carbon atoms or a phenyl radical optionally substituted by one or more identical or different halogen atoms, alkyl, trifluoroalkyl, alkoxy and / or alkyl mercapto groups, A is a straight or branched lower alkyl radical, Z is a Amino, alkylamino or dialkylamino group or a 5- to 8-membered saturated cyclic alkyleneimino group which may contain a further heteroatom and which may be substituted by alkyl, alkoxy, hydroxyalkyl, acyl or acyloxyalkyl groups, η is an integer from 3 to 7, m represents an integer from 0 to 4, which is characterized in that a dioxa-spiroalkane of the general formula II R- (CH ₂ ) -M

(III)

where R and m have the above meaning and M stands for an alkali atom or a —Mg-halogen group, expediently in an aromatic hydrocarbon or ether, converts the glycol monoether obtained after decomposition of the resulting complex in weakly acidic or neutral solution general formula IV

iCH ₂ ) _m -R

(CH ₂ ),

(IV)

(Π)

65 O-A-OH

in which A, R, m and η have the above meanings, converted in a manner known per se into a mesyl or tosyl ester and either this directly in a manner known per se with an amine of the general formula V

H-Z (V)

where Z has the above meaning, reacts or initially carries the mesyl or tosyl ester with it Sodium iodide is converted into the iodine compound and this is then added in a manner known per se without isolation the amine of the general formula V

H-Z

(V)

where A and π have the above meaning, with one in which Z has the above meaning.

The inventive method has the advantage over known methods that the yields in each process stage are almost quantitative and also relatively good in the glycol monoether formation stage Yields in the range from 48 to 90% can be achieved with a suitable choice of the reaction conditions mostly in the vicinity of about 90%.

The dioxaspiroalkanes of the general formula II to be used as starting materials can be prepared by methods known per se, for. B. by reacting cycloalkanols with corresponding alkanediols, in the presence of p-ToluoIsulfonsäuren as a catalyst, with azeotropic distillation (see. Ben 7IB, 1803, 1938) or in the presence of heavy metal catalysts, especially MoO ₃ , TiCU, SnCL, or AICl ₃ (cf. Compt rend. 251, 2191, 1960 and 255, 2978, 1962). According to more recent processes, such compounds have also been prepared using ion exchange resins and simultaneous azeotropic distillation. A method has also been described in which a corresponding cycloalkanone in dioxane solution in the presence of glycol sulfite is reacted with the glycol under the action of dry hydrogen chloride gas. (Chem. Ber. 93, 1249, 1960).

The first step of the process according to the invention, the implementation of the dioxa-spiroalkanes of the general Formula II with the organic metal compounds of the general formula III, whereby the I-alkyl, 1-aryl or l-aralkyl-l- (hydroxy-alkoxy) -cycloalkanes of the general formula IV are obtained completely new method; the possibility of this reaction is surprising, according to what is available sparse references (see Rec. Trav. Chim.

Pays-Bas 81, 238, 1962) the C-O bond of Compounds of the cyclic acetal type not split under the action of Grignard compounds will. The intermediates obtained in this way, which are glycol monoethers of the general formula IV new compounds not previously described in the literature.

The reaction of the dioxa-spiroalkanes of the general formula II with the organic metal compounds of the general formula III can be carried out in various ways. The reaction can be carried out in an aromatic hydrocarbon, advantageously in cumene, as the reaction medium; the Grignard compound of the general formula III can be prepared in situ in the reaction medium from the corresponding halide of the general formula

R- (CH ₂ ) _m -halogen

and made of metallic magnesium.

An ether, e.g. B. Diethyl ether can be used. After a special one advantageous embodiment of the process, the dioxa-spiroalkanes of the general formula II with organic magnesium halides of the general formula III in ethereal, advantageously dibutyl ethereal Solution implemented, then the ether is distilled off from the reaction mixture and the reaction in Benzene or another aromatic hydrocarbon.

The reaction of the compounds of general formula II with the Grignard compounds of General formula III obtained reaction products can then advantageously in weakly acidic or nearly neutral medium, expediently in aqueous ammonium chloride solution to the glycol monoethers of the general Formula IV can be hydrolyzed.

The compounds of general formula IV thus obtained are then z. B. with methanesulfonyl chloride or p-toluenesulfonyl chloride in the presence of a Acid binder, e.g. B. Pyridiri, converted into mesyl or tosyl esters and these directly with the Amines of the general formula IV converted to the end products of the general formula I.

One can mesyl or tosyl ester but also first with sodium iodide converted into the iodo compound, and then reacting this, without isolation with the amine of general formula V.

This procedure is particularly advantageous for the preparation of those basic ethers of the general formula I in which the basic group Z contains a hydroxyalkyl group as a substituent Product of the formula I can be obtained in very good yield.

The basic ethers of the general formula I prepared according to the invention can optionally by Distillation, advantageously be purified by fractional vacuum distillation. The basic ethers of the general form) I can, as known, with per se known solid or liquid carriers and / or auxiliary materials other than pharmaceuticals are used a

Some of the compounds of the general formula I which can be prepared according to the invention have already been described in the publications mentioned above, but some of them are new compounds. These also show valuable therapeutic properties; its spasmolytic effect exceeds the spasmolytic activity of papaverine many times over, but its toxicity is much lower and its ability to bind to the blood serum is also more advantageous. These compounds are therefore very suitable both for oral administration and for long-term treatment. They are also tranquillizers and show central sedative effects. Its infiltrative local anesthetic effect exceeds that of the well-known lidocaine. They are also more advantageous than papaverine with regard to other properties (lowering of blood pressure and peripheral vasolilatory effect); even in extremely high doses they show no carditoxic effect. In addition, these compounds show an advantageous coronary-dilating action which corresponds to that of prenilamine.

The process according to the invention is illustrated in more detail by the following examples.

example 1

ai) A mixture of 12.15 g (0.5 mol) of magnesium turnings, 300 ml abs. Benzene or toluene, xylene or isopropylbenzene and 0.5 mol of a dioxa-spiroalkane of the general formula II is mixed with a few iodine crystals when hot; then be under Stir and slowly reflux, within 2 hours 0.5 mol of a compound of general formula

R- (CH ₂ ) _m -halogen,

in which R and m have the meanings given above, added. The mixture is refluxed for a further hour, then, after cooling, shaken with 300 ml of saturated ammonium chloride solution. The separated organic phase is dried over anhydrous magnesium sulfate, evaporated and the residue in vacuo fractionated The obtained as the main fraction 1-alkyl-, 1-aryl or l-aralkyl-I- (w-hydroxyalkoxy) -cycloalkane, by repeated fractional vacuum distillation continued getting cleaned. Yield: 48 to 74%.
a ₂ ) The one from 14.4 g (0.6 mol) of magnesium and 0.6 mol

R-tCHjJm-halogen

in abs. Ether-produced Grignard compound of general formula III is mixed with 03 mol of dioxa-spiroalkane of general formula II. The excess of the ether is then distilled off; after an internal temperature of 80 to 90 ^° C. has been reached, the heating is switched off and the reaction mixture is allowed to cool to room temperature. The complex obtained is decomposed by shaking the reaction mixture with aqueous ammonium chloride solution, the separated aqueous phase is extracted with ether and the combined ethereal phases are evaporated. receive;

a3) From 60 g [0.86 g-atom] lithium and 0.4 mol of a Compound of the general formula

R- (CHz) _1n -Cl

is in 300 ml abs. Ether or petroleum ether, bp. 60 to 70 ⁰ C, an organic lithium compound of the formula

R- (CH ₂ ) _ro -U
manufactured. The reaction mixture obtained is on

cooled to a temperature below + 5 ° C and in 2 hours the solution of an equivalent amount of a dioxa-spiroalkane of the general formula II in 50 ml of abs. Benzene is added dropwise, then the reaction mixture is heated to boiling in a further 2 hours and refluxed for 1 hour. After cooling, the lithium alcoholate is decomposed with 50 ml of ice water, the organic phase is separated off, dried over anhydrous magnesium sulfate and evaporated. After fractionated vacuum

Table I.

distillation of the residue is the corresponding product of the general formula IV with yields of 64 to 90% received.

The starting compounds of the general formula II used in the above processes were prepared by the method described in Reports, 71 B, 1803 manufactured.

connection

Kpimm ed

F.

1,4-Dioxa-spiro- [4,4] -nonane 45 ° C / 10 -

1,4-Dioxa-spiro- [4,5] -decane 46 ° C / 3 -

1,5-Dioxa-spiro- [5,5] -undecane 75 ° C / 6-34 ° C

1,4-Dioxa-spiro- [5,6] -dodecane 76-80 ° C / 1,5 -

1,4-Dioxa-spiro- [4,7] -dodecane 108 ° C / ll -

The glycol monoethers of the general formula IV given in Table II below were prepared by the method described in Examples lai) - Ia3).

Table II

connection

Kpymm ed yield Methi 188 ° C / 6.5 58-63% ai 170 ° C / 3rd 64-67% Ά3 158-65 ° C / 2 60-65% a2 155-156 ° C / 3 74-80% ai, Ά2 168 ° C / 4th 48-50% ai 150-160 ° C / 4 60-65% a2 152-4 ° C / 0.2 60-65% ai, a2 128 ° C / 1st 80-90% 33 142-4 ° C / 0.2 80-84% a2 158-62 ° C / 0.2 76-82% a2 149_51PC / 0.15 80-87% a2 170 ° C / 0.6 60-63% a2

I [p-chlorophenyl-1 - (2'-hydroxy-ethoxy)] - 'cyclopentane

1 - Dodecyl-1 - (2'-hydroxy-ethoxy) -cyclopentane

I - (p-chlorobenzyl) -1 - ^ '- hydroxy-ethoxy-cyclopentane

I - Benzyl-1 - (2'-hydroxy-ethoxy) -cyclohexane

I (p-chlorophenyl) -1 - ^ '- hydroxy-ethoxyj-cydohexane

1 (p-chlorobenzyl) -1 - (2'-hydroxy-ethoxy) -cyclohexane

I (p-chlorophenyl) -1 - (3'-hydroxy-propoxy) -cyclohexane

l-amyl-l- (3'-hydroxy-propoxy) -cyclohexane

I - Benzyl-1 - (2'-hydroxy-ethoxy) -cycloheptane

I (p-chlorobenzyl) -1 - (2'-hydroxy-ethoxy) -cycloheptane

1 - Benzyl-1 - (3'-hydroxy-propoxy) -cycloheptane

I (p-chlorobenzyl) -l - ^ '- hydroxy-ethoxyj-cyclooctane

bi) 0.2 mol of a glycol monoether of the general formula IV are abs in 200 ml. Pyridine dissolved and 38.1 g (0.2 mol) of p-toluenesulfonyl chloride added in your portions at) ° C. The mixture is stirred at room temperature for 2 hours, then poured onto 500 g of lis. The mixture is extracted with 100 ml of chloroform three times, the combined Chloroormextrakte with 200 ml of water five times, lann the organic phase over anhydrous calcium chloride is dried, treated with activated carbon ind evaporated. The corresponding p-toluenesulfonic acid ester is obtained in the form of a viscous yellowish-red oil with an almost quantitative yield. This raw product can be used immediately without cleaning .

° 2) 3 g (0.1 mol) of sodium amide in 30 ml of abs. tenzene is suspended and a solution of an equivalent amount of a glycol monoether of the general formula IV in 30 "ml of absolute benzene is added dropwise while stirring. The reaction mixture is refluxed for 1 hour, then cooled to at least 20 ° C and slowly added at 19 ° 0.1 mol) of p-toluenesulfonyl chloride replaced The reaction mixture is stirred for 3 hours at 'constant temperature, then washed acid-free with aqueous sodium bicarbonate solution, washed over

eggs dried magnesium sulfate and at 50 ° C im 'vacuum evaporated. The as residue in almost

45

55

The ester obtained in quantitative yield can be used further without purification.

03) 4.6 g (1.2MoI) finely chopped sodium metal are mixed with 03MoI of a glycol monoether of the general formula IV in 300 ml of abs. Benzene under stirring until complete dissolution of sodium (about 10 to 16 hours) under reflux Then the reaction mixture to 5 ⁰ C is cooled at 5 to 10 ° C with 38.1 g (0.2 mol) of p-toluenesulfonyl chloride in small portions are added and the mixture is stirred at room temperature for 1 hour. The benzene solution obtained is then extracted with 300 ml of water, the separated organic phase is dried over anhydrous calcium chloride, treated with activated charcoal and evaporated can be used in the next synthesis step.

c) 0.1 mol of a tosyl ester prepared according to Example Ib-Ib ₃ ) is abs in 50 ml. Dissolved acetone and with a solution of 15 g (0.1 mol) of sodium iodide in 50 ml of abs. Acetone is added. The mixture is left to stand at room temperature for 24 hours, then the crystalline sodium p-toluenesulfonate is filtered off; the iodine compound obtained in the acetone filtrate can be used immediately, without isolation or after evaporation of the solution and taking up in another solvent

609528/479

tel can still be used. The one based on p-toluenesulfonic acid calculated yield is almost quantitative.

di) 0.1 mol of a 1-aryl-, 1-aralkyl- or 1-alkyl- 1- (u) -hydroxyalkoxy) -cycloalkan-tosyl ester prepared _{according to example lbi-lb 3) is 0.25 to 0,} 6 mol of a primary or secondary amine of the general formula V are added (solid or gaseous amines are used in a benzene, toluene or xylene solution). The mixture is left to stand at room temperature for 24 hours. The reaction mixture is then poured into water, the organic phase is separated off and evaporated and the residue is fractionated in vacuo. The desired basic ether is obtained as the main fraction with an almost quantitative yield.

Example for the direct implementation of the

Tosyl ester of a compound of the formula IV with

an amine

44.9 g of 1-benzyl-1 - ((- hydroxypropoxyj-cycloheptantosylate are dissolved in 150 ml of anhydrous toluene. So much dimethylamine gas is then put into this solution initiated until 18 g are dissolved. The reaction solution is then left to stand at room temperature for 24 hours and after this time poured into cold water. The organic phase is separated off, evaporated and the remaining red oil is fractionally distilled. Yield about 90%. Boiling point: 164-165 ° C / 3 Torr.

The basic ether of the general formula I obtained as the reaction product can optionally be used for Gas activation can also be converted directly into an acid addition salt without distillation, e.g. B. in the in the following way:

0.1 mol of the crude basic amine is dissolved in 50 ml of alcohol, the solution is treated with activated charcoal and then added to a hot solution of 11.6 g (0.1 mol) of fumaric acid in 150 ml of water. The mixture is cooled immediately, left to stand in the refrigerator for 12 to 48 hours, then the crystals obtained are filtered off, dried and recrystallized from acetone or from a mixture of acetone and ethanol or acetone, ethanol and gasoline. In this case, too, the corresponding salt is obtained with an almost quantitative yield,
dz) 0.1 mol of the 1-aryl-, 1-aralkyl- or 1-alkyl- l- (ö) -iodoalkoxy) -cycloalkane obtained according to Example Ic) is also used in acetone solution with 0.2 mol of one secondary amine dissolved in acetone and left to stand for 24 hours at room temperature. Then the acetone solution in 400 l of water

poured and the excreted oil with 2 x 50 ml Benzene extracted The benzene extracts are combined, the solvent evaporated and the residue Purified by distillation. When reacting with primary amines, the above-mentioned acetone becomes Solution evaporated, the residue dissolved in 100 ml of benzene and this solution to react with the amine used. The separated amine hydroiodide is removed by filtration, the benzene filtrate as The product obtained residue is purified by fractional distillation in vacuo Ethers were characterized as salts. They are listed in Table IH below

Table III

connection

KpVmm Hg

F.

1 -p-chlorophenyl-1 - ^ '- diethylaminoethoxyj-cycloheptane hydrochloride 1 -p-chlorophenyl-1 - ^ '- piperidinoethoxyj-cycloheptane hydrochloride 1 -p-chlorophenyl-1 - [2 '- (I "-0-hydroxyethyl-4" -piperazinyl) ethoxy] -cyclo-

pentene difumarate
1-Dodecyl-1 - [2 '- (I "- / J-hydroxyethyI] -4" -piperazinyl) ethoxy / cyclopentane fumarate

1-p-chlorophenyl-1 ^ 'räthylaminoäthoxyj-cyclopentane hydrochloride l-Benzyl-l - ^ '- dimethylaminoethoxyJ-cyclohexane hydrochloride l-Benzyl-l - ^ '- diethylaminoethoxy / cyclohexane hydrochloride 1 -Benzyl-1 - ^ '- piperidinoethoxyj-cyclohexane hydrochloride l-p-Chlorobenzyl-l- (2'-diethylaminoethoxy) cyclohexane hydrochloride l-p-Chlorobenzyl-l- [2 '- (l "-methyl-4" -piperazinyl) ethoxy] cyclohexane hydrochloride

1 -p-chlorophenyl-1 - ^ '- dimethylaminoethoxyj-cydohexane hydrochloride 1 -p-chlorophenyl-1 ^ '- diethylaminoethoxyj-cyclohexane hydrochloride 1 -p-chlorophenyl-1 - ^ '- piperidinoethoxyj-cyclohexane hydrochloride 1 -p-chlorophenyl-1 - ^ '- morpholinoethoxy ^ cyclohexane hydrochloride 1 -p-chlorophenyl-1 - [2 '- (I "-methyl-4" -piperazinyl) ethoxy] cyclohexane

hydrochloride
lp-chlorophenyl-l- [3 '- (l "-methyl-4" -piperazinyl) -propoxy] -cyclohexane

hydrochloride
lp-chlorophenyl- [3 '- (l "-benzyl-4" -piperazino) propoxy / cyclohexane hydrochloride

1 -p-chlorophenyl-1 - (S'-diethylaminopropoxy / cyclohexane hydrochloride l-p-Chloφhenyl-l- (3'-piperidinopropoxy) -cyclohexan-hydΓOchlorid 1 -p-chlorobenzyl-1 - ^ '- piperidinoethoxyj-cyclohexane hydrochloride l-p-chlorophenyl-l- [2 '- (r'-ß-hydroxyethyl-4' '- piperazinyl) ethoxy] -cyclo-

hexane difumarate
1-p-chlorobenzyl-1 - [2 '- (I "- /? - hydroxyethyl-4" -piperazinyl) ethoxy] cyclohexane difumarate

140-145 ° C / 0.4 138 170-180 ° C / 0.2 176 180 170-175 ° C / 0.6 172-173
122 120-133 ° C / 0.2 134-135 130-136 ° C / 0.25 118-120 154-160 ° C / 0.1 l 181 155-160 ° C / 0.1 l 149 192-197 ° C / 0.1 l 198-199 140-146 ° C / 0.4 177-179 145-152 ° C / 0.8 146 169-175 ° C / 0.5 182 188-190 ° C / 03 179 194-196 ° C / 0.8 215-216 H2O 180-185 ° C / 0.05 239 1/2 H2O 240-250 ° C / 0.4 221 180-187 ° C / 0.6 178 180-185 ° C / 0.2 221-222 155-160 ° C / 0.5 180-181 194 - 185-186

11th

continuation

Connection . Kp7mm Hg F.

1 -p-chlorophenyl-1 - [2 '- (1 "-dehydroxyethyl-4" -piperazinyl) ethoxy] -cydo-

hexane difumarate
1 - Amyl-1 - [3 '- (1 "- ^ - hydroxyathyl ^ -piperazinylj-propoxyj-cyclohexane

difumarate
1-Benzyl-1- [3 '- (I "- / S-hydroxyäthyI-4" -piperazinyl) propoxy] cycloheptane

difumarate
1-p-chlorobenzyl-1- [2 '- (I "- /? - hydroxyethyl-4" -piperazinyl) -ethoxy] -cyclo-

heptane difumarate

l-p-chlorobenzyl-l - ^ '- methylaminoethoxyJ-cycloheptane fumarate i-Benzyl-l- [2 '- (l "- / 3-hydroxyethyl-4" -piperazinyl) ethoxy] cycloheptane

difumarate

1 -Benzyl-1 - (3'-cyclohexylaminopropoxy) -cycloheptane fumarate 1 -Benzyl-1 - (S'-diethylamino-ethylaminopropoxyJ-cycloheptane difumarate l-Benzyl-l-p'-methylamino-ethoxy / cycloheptane fumarate 1 -Benzyl-1 - (S'-methylamino-propoxyJ-cycloheptane fumarate l-Benzyl-l - ^ '- dimethylamino-ethoxyJ-cycloheptane fumarate 1-Benzyl-1- (3 "-dimethylaminopropoxy) -cycloheptane fumarate 1 -Benzyl-1 - ^ '- diethylamino-ethoxyj-cycloheptane hydrochloride l-Benzyl-l-p'-diethylaminopropoxyJ-cycloheptane fumarate 1-Benzyl-1- (2'-diizopropylaminoethoxy) -cycloheptane fumarate 1-Benzyl-1-p'-heptamethylene iminopropoxy / cycloheptane fumarate l-Benzyl-l - ^ '- morpholino-propoxyJ-cycloheptane fumarate 1-p-chlorobenzyl-1 - (^ '- dimethylaminoethoxyj-cycloheptane fumarate 1 -p-chlorobenzyl-1 - (2'-diethylaminoethoxy) -cycloheptane fumarate 1 -p-chlorobenzyl-1 - ^ '- diisopropylaminoethoxyj-cycloheptane fumarate 1-p-chlorobenzyl-1 - (2'-diethylaminoethoxy) -cyclooctane hydrochloride 1 -p-chlorobenzyl-1 - (2'-piperidinoethoxy) -cyclooctane hydrochloride 1 -p-chlorobenzyl-1 - [2 '- (I "-jS-hydroxyethyl-4" -piperazinyI) -ethoxy] -cyclo-

octane difumarate

- 188 - 185-186 - 173-174 - 179-180 152-157 ° C / 0.2 145-146 - 176 176-182 ° C / 0.2 158-159 179-18FC / 0.2 134-135 130-138 ° C / 0.2 150-151 146-152 ° C / 0.3 128-129 154-162 ° C / 3rd 134-135 142-146 ° C / 3rd 133-134 169-171 ° C / 4 120-121 183-185 ° C / 4 92-93 168-170 ° C / 2 118-119 130-134 ° C / 2 113-114 194 ° C / 2nd 128-129 169-83 ° C / 4 122-123 174-177 ° C / 3 112-113 199-201 ° C / 3rd 106-107 176-178 ° C / 0.2 167-168 180-200 ° C / 0.4 190 193-194

Claims (1)

Patent claims: 1. Process for the preparation of basic ethers of the general formula I. CH ₂ ) -R Ο —Α —Ζ Sodium iodide converted into the iodine compound and this then without isolation in a known per se Way with the amine of the general formula V