IL22302A - Phenylcyclopropane derivatives - Google Patents

Description

Phenylcyelopropane derivatives 2 invention to derivatives and to processes for their o present invention may represented by the whereinί is or is amino or a alkoxy is a straight or branched alkyl radical containing a least 2 carbon phenyl or hydroxy lower alkyl radical or when is may be an is hydrogen or a or branched alkyl radical o hydroxy lower alkyl or and together with nitrogen to they are a saturated heterocyclic he of compounds falling within formula illustrative of the new compounds according to the wherein and have same as i formula 3 22302 2 wherein and are as previously and wherein is a straight or branched radical or a lower alkyl and R and are as defined The compounds of formulae III and IV form salts with acids and these acid addition salts are also within the scope of this The compounds of formula IV form quaternary nium salts and these quaternary ammonium salts are also within the scope of this The compounds of this invention may exist as cis or trans It is intended to include in this invention the separated cis and trans isomers as well as the mixtures At present the trans isomers appear to have particularly advantageous activity and these are therefore The compounds of this invention can be prepared by various methods which are practicable and capable of supplying the desired derivatives in good In accordance with a preferred the compounds of formula II are prepared by the following synthetic n is 0 or 1 and and are aa defined This reaction is carried out by adding the carbonyl chloride to the or to the amine at a temperature of from to and in the presence of an acid binding such as an excess of the amine or such as a an or an alkali metal or alkaline earth metal carbonate or She carbonyl chloride the amine may be dissolved in a suitable such as ethyl benzene or a mixture Alternatively the carbonyl chloride can be added to a concentrated aqueous solution of the After bringing the the reaction is completed by stirring the reaction mixture at a temperature of from to preferably at room for a period for from 15 minutes to 11 In accordance with a second compounds of formula in which is and R and are as defined are prepared according to the following This reaction is best carried out by heating the reactants in the presence of a polar such as water or a lower in a sealed tube at a ture of from to An advantageous method for the preparation of the compounds of formula III and IV is the reduction of the corresponding compounds of formula This reduction can be carried out by reacting the amide with lithium aluminium hydride in a suitable such as dry ethyl toluene or at a temperature of to for period for from 1 to 24 The compounds of III and IV can also be prepared by the following wherein and are as defined In this method the ethyl carboxylate is reduced to the alcohol for lithium aluminium hydride in a suitable such as dry ethyl The alcoholic hydroxy group is replaced by chlorine by treatment for a phosphorus or thionyl and the resulting alkyl chloride then aminated in the presence of an acid binding Alternativel the compounds of IV can be prepared by reacting a compound of where R and are as defined above with a suitable lating for an acyl and reducing the product or an alkylating agent such for an alkyl acid addition salts of this invention can be prepared in the usual that is by reacting an amine of formula III or IV with an inorganic for or sulphuric or an organie for salicylic or citric The quaternary ammonium salts of this invention can also be prepared in conventional manner by reacting an amine of formula IV with a lower such as methyl bromide or methyl The novel phenylcyclopropane derivatives of the present invention exhibit significant pharmacological properties and fairly low A close relationship between structure and activity has been established for the members of homologous The substituted amino derivatives depending upon the nature of the the property of stimulating the central nervous system affecting the peripheral vegetative section providing activity and or remarkable activity activity appetite depressing antimycotic The amido derivatives exhibit antispasmodic activity activity as central nervous system The novel compounds of this invention can be administered suboutaneously or intravenously in any of the known pharmaceutical forms generally employed for these modes of The following examples are given by way of tration EXAMPLE ΐ trans 30 g of trans carbonyl chloride were added to 54 g of 70 per cent aqueous During this addition the temperature of the reaction mixture was kept below After the addition was the mixture was stirred for one hour and allowed to warm up to room The mixture was then poured into 200 cc of The pitate was collected by washed with water until the wash water no test for chloride and dried at in g per cent of the theoretical The product was purified by tallization from ethyl for Pound By the same method the following compounds were prepared in which the phenyl radical bore a if the correspondingly substituted starting material was trans trans its hydrochloride salt melts at 2 ns trans anecarbonamide EXAMPLE 2 g of thionyl chloride in 160 cc petroleum ether was added with to a suspension of 40 g of cis eyclopropanecarboxylic acid in 160 cc of petroleum ether kept below After the addition was the mixture was stirred for one hour and allowed to warm up to room Removal of the petroleum ether under reduced pressure orange oily cis propanecarbonyl preparation is a little different from that described by and arkas The chloride was dissolved in 100 ce of anhydrous ethyl ether and added with to a solution of 28 g of in 250 co of anhydrous ethyl During this addition the temperature of the reaction mixture was kept below After the addition was the mixture was for one hour and allowed to warm up at room After standing the precipitate was removed by filtration and washed with ethyl The combined filtrate and ethereal washings were treated with 100 cc of I sodium washed with water the wash water gave no test for chloride dried over filtered and decolorized with carbon Evaporation of the solvent left a solid product that was purified by crystallisation from propyl A mixture of g of trans ethyl 12 g of and 20 cc of ethyl alcohol was heated at in a sealed After about 10 hours ethyl alcohol was removed from the reaction mixture by distillation under reduced The residue was dried at in vacuo and crystallized from The product s purified by ion from ethyl for Found trans The procedure of Example 1 was repeated by reacting 40 g of trans chloride with 50 g of 50 per cent The product was purified by crystallization from ethyl for Found EXAMPLE 5 trans 15 g of trans canbonyl chloride were added with to a mixture of 9 g of chloride and 40 cc of During this addition the reaction mixture was ke below After the addition the mixture was stirred for three hours and allowed to warm up to room The mixture was allowed to stand and the excess of pyridine was distilled off under reduced The residue was washed with water until the wash water gave no test for chloride and dried at in 15 g per cent of the theoretical The product was purified by crystallization from ethyl Pound EXAMPLE trans g o trans earbonyl chloride were added with to a solution of g of isobutylamlne and 18 g of anhydrous During this addition the temperature of the reaction mixture was kept below After t e addition was the mixture was heated to about and stirred for 15 The solution was allowed to cool slowly to room with and was then poured into 100 cc of The cipitate was collected b washed with water until the wash water gave no test for chloride and dried at in g per of the theoretical She product was purified by crystallization a solvent mixture of ethyl alcohol and for In an analagous manner the following compounds were prepared from the corresponding starting 199 trans mide EXAMPLE 7 trans solution of 10 g of trans eyclopropanecarbonyl chloride in 50 cc of anhydrous acetone was added with to a solution of g of and g of anhydrous triethylamine in 50 cc of anhydrous During this addition the temperature of the reaction mixture was kept below After the addition the mixture was stirred for two hours and allowed to warm up to room The precipitate was by filtration and washed with The combined ltrate and washings were washed with w ater until the wash water gave no test for chloride The solvent was removed and the residue was dissolved in 100 cc of After washing with H and with the solution was decolorized with carbon concentrated to 40 cc by boiling and allowed to The precipitate was collected by g per cent of the theoretical The product was purified by crystallization from for Found EXAMPLE 8 A solution of 10 g of trans cyclopropanecarbonyl chloride in 50 cc of anhydrous benzene with to a solution of g of utylamlne and g of anhydrous in 50 cc of anhydrous During this addition the temperature of the reaction was kept After the addition was the mixture was stirred for two hours and allowed to up to room The precipitate was removed by filtration and washed with The combined filtrate and washings were washed with water until the wash water gave no test for chloride The solvent was removed by distillation at irst at atmospheric pressure and then under reduced 7 per the The product was purified by crystallization from isopropyl for Found EXAMPLE trans The procedure of Example 6 was repeated by reacting 15 g of trans with a mixture of g of amine and 13 g of anydrous g per cent of the theoretical The product was purified by crystallization from ethyl for Found EXAMPLE 10 The procedure of Example 6 was by ing 20 g of trans chloride with a mixture of g of hexylamine and of anhydrous g per cent of the theoretical The product was purified by crystallization from isopropyl for Pound EXAMPLE 11 trans A solution of 15 g of trans cyclopropanecarbonyl chloride in 15 cc of anhydrous benzene was added with to a solution of of diethylamine in 200 cc of anhydrous During this addition the temperature of the reaction mixture was kept below After the addition the mixture was stirred for one hour at room The precipitate was removed by The was washed with aqueous hydrochloric acid and then with water until the wash water gave no test for chloride The benzene was removed by distillation under The oily residue was tionally distilled and the fraction boiling at mm was g per cent of the theoretical d n D for Found 22302 2 EXAMPLE 12 els procedure of Example 11 repeated by reacting a solution of 44 g of cis oyclopropanecarbonyl chloride according to the process in Example in 100 cc arfydrous ethyl ether with a solution of 54 g of diethylamide in 200 of anhydrous ethyl The product was purified by crystallization from isopropyl 58 for Found 13 trans procedure of 11 was repeated by reacting a solution of 15 g of trans propanecarbonyl chloride in 10 of anhydrous benzene with a solution of 21 g of in 200 cc of anhydrous Yield 15 g per cent of the theoretical mm d for Found 14 trans IDE A solution of 15 g of trans c clo ro anecarbonl chloride in cc of anhdrous ethl 2 ether was addled with to a solution of g of in 70 cc of drous ethyl this addition the temperature of the reaction mixture below this addition was stirred fo one hour and allowed to up to room The precipitate was removed by filtration washed with ethyl The combined filtrate and washings were washed with with hydrochloric acid and again with water until the wash water gave no test for chloride The solvent was removed by the oily residue was fractionally distilled and the fraction boiling at mm was g per cent of the theoretical d for ΕΧΑ 15 trans A solution of 15 g of propanecarbonyl chloride in 15 cc of acetone was added with to a solution of 14 g hydrochloride in g of anhydrous During this addition the temperature the reaction mixture was kept below After the addition was the mixture was stirred for eleven hours and allowed to up to room After standing the precipitate was removed by filtration and washed three times with 30 cc ortions f eth l The combined and were evaporated under reduced The residue was dissolved in anhydrous ethyl washed twice with 50 portions of IN and then with The solution was washed with water until the wash water gave no test for chloride ion and evaporated under reduced oil residue was dissolved in anhydrous and 13 g per cent of the theoretical amoun n for Pound St trans A solution of 0 g of propanecarbonyl chloride in 50 cc of anhydrous ethyl ether was added with to a solution of g of and g of amine in 50 cc of anhydrous ethyl During this addition the temperature was kept below After the addition was the mixture was stirred for two hours and allowed to warm up to room precipitate was removed by filtration and washed with ethyl combined filtrate and ethereal washings were washed at first with I and then with water until the wash water gave no test for chloride The product was recovered by evaporating the solvent under reduced g per cent of the theoretical product was purified by ization from isopropyl for Found 17 trans The procedure of Example 11 wag repeated by reacting a solution of 15 g of trans propaneoarbonyl chloride in 20 cc of anhydrous benzene with a solution of 23 g of in 100 cc of anhydrous g per cent of the theoretical o o d for Found EXAMPLE trans 30 g of trans carbonyl chloride were added with to a solution of g of in 27 g of anhydrous During this addition the ature of the reaction mixture was kept below After the addition was the mixture was stirred for one hour at pyridine was removed by oration and to the oily residue were added 100 cc of The oily layer after washing with 100 oc of hydrochloric acid and with water until the wash water gave no test for chloride was fractionally mm Yield g per cent of the theoretical d for In an manner the compound was pared from the corresponding starting materials trans mide mm 19 rans A solution of 10 g of propanecarbonyl chloride in 25 cc of acetone and 25 of ethyl ether was added with to a solution of g of morpholine and triehylamine in 25 cc of acetone and 25 cc of ethyl During this addition the temperature was below After the addition was the mixture was stirred for two hours and allowed to warm up to room The precipitate was by filtration and washed with a solvent mixture of acetone and ethyl The combined filtrate and washings were evaporated under reduced The oily residue was treated with N HC1 and then The solid was collected by washed with water until wash water gave no test for chloride and dried in vacuo at g per cent of the theoretical The product was purified b tallization from isopropyl for Found EXAMPLE 20 The procedure of Example 11 was repeated by acting a solution of 30 g of eyclopropanecarbonyl chloride in 40 cc of anhydrous benzene with a solution of 25 of 34 g per cent of the theoretical product was purified by crystallization from ethyl for Found EX 21 trans fE A solution of 10 g of trans phenylcyclopropanecarbonyl chloride in 30 cc of ethyl ether was added with to a solution of g of piperidine in 70 cc of anhydrous ethyl During this addition the temperature of the reaction mixture was below 10 After the addition was the was stirred for one hour and allowed up to room The precipitate was removed by filtration and washed with ethyl The combined filtrate and ethyl ether washings were at first with and then wit until the wash water gave no test for chloride After the solution been dried over the solvent was removed by distillation at first at atmospheric pressure and then under reduced g per cent of the theoretical The product was purified by crystallization from isopropyl for In an analogous manner the following compound was prepared from the corresponding stalling trans which has been fractionated in a rotary film evaporator at 120 its hydrochloride salt melts at EXAMPLE 22 trans IPE The procedure of Example 19 was repeated by acting 20 g of trans carbonyl chloride in 50 cc of anhydrous ethyl ether with a solution of g of and g of triethylamine in 150 cc of hydrous ethyl g per cent of the theoretical mm for Found EXAMPLE trans A solution of 20 g of trans phenylcyclopropanecarbonamide as described in Example in 50 cc of anhydrous tetrahydrofuran was added with to a suspension of g treated a mixture of 40 cc of water and 100 cc of The precipitate was filtered off and washed with The combined filtrate and washings were acidified with sulphuric The solvent was evaporated and the residue diluted to 160 cc wit The aqueous solution was washed with benzene and rendered alkaline with 20 g of solid potassium The oily layer was extracted with ethyl dried over sodium sulphate and evaporated under reduced The residue was dissolved with The benzene was then removed by distillation and the oil was distilled under reduced mm d titrimetric value HYDROCHLORIDE To a solution of 2 g of the base prepared as described above 20 cc of ethyl alcohol was added an excess of hydrogen chloride dissolved in ethyl The tion was allowed to stand overnight at the tate was collected by washed with ethyl dried in vacuo and recrystalllzed from a solvent mixture of ethyl ether and ethyl for Found EXAMPLE 24 pis A solution of g of cis carbonamide described in Example in 50 cc of anhydrous tetrahydrofuran was added with to a suspension of 2 g of in 100 cc of anhydrous After the addition was the suspension was refluxed for sixteen allowed to cool to room temperature and added to a mixture of 30 cc of water and 30 cc of The product was recovered in the same manner as described in Example 23 mm n cis HYDROCHLORIDE The hydrochloride salt was prepared in the same manner as described in Example 23 EXAMPLE trans g of trans pane as described in Example were reduced by the procedure described in Example 23 reduction being carried out for 14 Yield 93 mm d trans HYDROCHLORIDE To a solution of 4 g of the base in 100 ce of acetone was added an excess of hydrogen chloride dissolved in ethyl precipitate was redissolved by warming and allowed to crystallize at The crystals were collected by washed with ethyl dried in vacuo and reerystallised from for Found trans g of as described in Example were reduced by the procedure described in Example 23 the reduction taking 14 mm value trans HYDROCHLORIDE The hydrochloride salt was prepared in the same manner as described in Example 23 for Found In an anagous manner the following compound was prepared from the corresponding starting trans whose hydrochloride salt melts at 27 trans g of trans carbonamide as described in Example reduced by the procedure described in Example 23 the reduction taking 12 Yield g mm mm n value trans The hydrochloride salt was prepared in the same manner as described in Example 23 Analysis for Found EXAMPLE 30 Fourteen hours were required for the reduction of g of trans described in Example by the procedure described in Example mm titrimetric value trans hydrochloride salt was prepared in the same manner as described in Example 23 and purified by reorystalllzation from a solvent mixture of ethyl ether and ethyl for Found EXAMPLE 31 trans Two hours were required for the reduction of 13 g of trans carbonamide described in Example by the procedure described in Example mm titrimetric value trans To one molar equivalent of the base in anhydrous ethyl alcohol was added more than one equivalent of hydrogen chloride dissolved in ethyl ether The precipitate was collected by washed with ethyl dried in vacuo and recrystallized from a solvent mixture of ethyl ether and ethyl for Found EXAMPLE 32 trans g of trans as described in Example were placed in a porous thimble and a suspension of g of 300 cc of tetrahydrofuran was placed in the flask of a continuous The suspension was refluxed for ten The flask was then immersed irian freezing mixture and to the cooled reaction mixture was with a mixture of 50 cc of water and 50 cc of The precipitate was collected by filtration and washed with The combined filtrate and washings were acidified with 60 cc of sulphuric acid and the solvent was removed by the residue was dissolved in 200 cc of water and washed with cc of chloroform and then with 200 cc of ethyl aqueous solution was cooled to and rendered alkaline with 100 g solid potassium oily layer was extracted three times with ethyl ether using a total of 300 ethereal solution was dried over sodium sulphate and ated under reduced pressure to remove the residue was dissolved in 60 cc of The benzene was then removed by distillation and the oil was distilled under reduced o titrimetric value trans The hydrochloride salt was in the same manner as in Example 23 204 for Found 33 trans A solution of 6 g of chloride in 24 cc of benzene and 30 cc of were dropped simultaneously into a solution of 6 g of trans hydrochloride in 110 cc of water and 50 cc of kept below After the addition was the mixture was stirred for two and allowed to warm up to room After the layer was separed from the benzenic layer and was washed with 40 ec of ethyl The combined benzenic layer and ethereal washings were washed with and water until wash water gave no test for chloride The solvents were removed by Yield g per cent of the theoretical The product was purified by crystallization from for Found 34 trans g of chloride were dissolved in 70 cc of anhydrous acetone and 70 cc of ethyl The solution was slowly with into a solution of g of trans and g of triethylamine in 110 cc of anhydrous ethyl During this addition temperature of the mixture was below After standing the precipitate was removed by filtration and washed with a solvent mixture of acetone and ethyl The combined filtrate and washings were evaporated under reduced The oily residue was dissolved in 70 cc of ethyl the solution was washed with sodium hydroxide and water until the wash gave no test for chloride The solvent was removed by 20 The product was recrystallized from isopropyl for Pound EXAMPLE 35 l g of trans me h laminometh phenyieyclopropane g of and of potassium hydroxide were heated at about in a sealed After eight hours the tube was the reaction mixture was washed twice with 20 cc portions of ethyl ether and the residual inorganic salt was dissolved in 30 oc of aqueous liquor was washed with 30 cc of ethyl The ethereal extracts were combined and dried over potassium Thereafter the solvent was removed by The oily residue was dissolved in 20 cc of After removing of benzene by evaporation at atmospheric the residue was fractionated under 37 mm ric value n for Found EXAMPLE 36 trans A solution of 15 g of phenylcyclopropanecarbonamide as described in Example in 20 cc of ethyl ether and 20 cc of toluene was dropped into a suspension of g of in 7 cc of ethyl ether and 75 cc of toluene which had been heated to After the addition was continued for three The reaction mixture was poured into 50 cc of The organic layer was separated in a separator funnel and the aqueous layer was extracted three times with ethyl using a total of 300 The combined organic layer and ethereal extract were ated and the oily residue was fractionated under reduced 9 mm d J value trans HYDROCHLORIDE A solution of g of the base in 20 cc of anhydrous ethyl ether was cooled to and the space above the solution was filled with To this solution was added hydrogen chloride dissolved in ethyl ether until the solution was acid pH strongly hygroscopic precipitate was collected carefully by filtration and dried in for Found trans YL0YCL0PR0PAHE PICRATE The picrate salt was prepared in the usual way and purified by crystallization ethyl EXAMPLE 37 The procedure of Example repeated by reflux for hours a solution of 20 g of as closed in Example 1 i 100 cc of anhydrous ethyl with g of 100 cc of anhydrous ethyl gi mm d n J ti value E Was prepared in the usual way and purified by crystallization from ethyl 58 A mixture of g of trans cyclopropanecarbonyl chloride in 20 cc of anhydrous acetone and 20 cc of anhydrous ethyl ether was with into a solution of of trans as disclosed in Example and g of anhydrous triethylaniine in 40 cc of anhydrous ethyl During this addition the temperature of the reaction mixture was kept After the addition was the mixture was stirred for three hours and allowed to warm up to room S mixture was then filtered and the precipitate was washed with a solvent mixture of acetone and ethyl The combined filtrate and washings were evaporated under reduced The oily residue was dissolved in 50 cc of ethyl ether and the was washed at first with then hydrochloric acid and at last with water until water gave no test chloride Thereafter the solution was dried over sodium sulfate and The oily residue was distilled under reduced n for Pound 39 A solution of g of phenyicyclopropane as disclosed in Example in 20 cc of anhydrous tetrahydrofuran was dropped with stirring into a suspension of 2 g of in 50 ce of 4 hydrous After the addition was the suspension was refluxed for three allowed to cool and added to a mixture 15 cc of water and 15 cc of The product was recovered in the same manner as disclosed in Example 23 Yield value 40 trans The procedure of Example 36 was repeated by refluxing for four hours a solution of 12 g trans lcyclopropanecarhonaiaide as disclosed in Example in 50 cc of anhydrous ethyl ether with a suspension of g of in 100 of anhydrous ethyl gi titrimetric value for Found trans solution of of trans as described in in 15 ce of benzene and 15 co of ethyl ether added with to a sion of in cc of ethyl 0 cc of benzene at such a rate that the temperature never exceeded After the addition was the mixture was for three cooled to and poured into 20 cc of organic layer was separated and the aqueous liquor was extracted three times with 50 ce portions of ethyl the organic layer and the ether extracts were combined and the solvents were distilled The oily residue was fractionated under reduced g mm titrimetric value for he was prepared in the usual way and by crystallization from ethyl g of cyelopropane and g of methyl iodide were heated at about a sealed tube filled with After five the tube was allowed to stand at room temperature for tube was then broken and the product dried in vacuo at room temperature for 72 hours and then in a drying pistol at for 5 dried residue was dispersed in ethyl collected by washed with ethyl acetate and petroleum ether and dried in for Found Ϊ EXAMPLE 42 trans The procedure of Example 41 was repeated by reducing 15 g of trans cyclopropanecarbonamide as disclosed in Example 10 mm metric value d The procedure of Example 41 was repeated b reducing 13 g of trans carbonamide as described in Example gs mm d n titrimetric value HYDROCHLORIDE The hydrochloride salt was prepared in the same manner as described in Example product is strongly hygroscopic Analysis for Found PICROMA E The picrolonate salt was prepared in the usual and purified by crystallization from ethyl In an manner the following compounds were prepared from the corresponding starting materials trans clopro at trans whose hydrochloride salt melts at ans The methyl iodide quaternary salt was prepared in the same described in Example 41 and crystallisation from ethyl Analysis for Found s Έ was prepared according the following A solution of of trans in 50 cc of chloroform was with into a solution of g thionyl cloride in 50 cc of After the addition was the reaction mixture was refluxed for one hour and a The solvent and the unreacted thionyl chloride were removed by The residue was dissolved with 20 cc of benzene the solution was fractionated under 10 of trans for Found 4 g of and g of in cc of xylene were refluxed The reaction mixture was cooled and the precipitate was removed by solution was washed with 1 he solvent was evaporated and the oily residue was 1 ducing 17 of as described in Example 14 titrimetric value trans procedure of was repeated by ducing 15 g of trans carbonamide as described in Example value EXAMPLE 46 trans The procedure of Example 36 was repeated by reducing g of trans propanecarbonamide as disclosed in Example trans CYCLOPROPANE A mixture of 30 g trans g of and 10 cc of ethyl alcohol was heated at in a sealed After about 24 hours the ethyl alcohol and the unreacted products were removed from the reaction mixture by distillatio under reduced pressure at g of the residue was dissolved in 30 cc of anhydrous tetrahydrofuran and added with to a suspension of g in 50 cc of anhydrous During this Edition the temperature of the reaction mixture was kept below After the addition was the suspension was reflu fo allowed to cool to room and treated with a mixture of 30 cc of water and of tetrahydro The precipitate was filtered off and washed with The combined filtrate and washings were acidified with 15 cc of solvent was The residue was washed at first with chloroform and then with ethyl The was rendered alkaline with anhydrous potassium carbonate and the layer extracted with ethyl ethereal solution was dried over sodium sulphate and evaporated under reduced The oily residue was dissolved with The benzene was removed by distillation and the oily residue 180QC titrimetric value for i Found EXAMPLE trans The procedure of Example was repeated by reducing 15 g of as described in titrimetric value trans The hydrochloride salt prepared in the same manner ad described in Example 36 and purified by crystallisation 3 a solvent of ethyl ether and ethyl for trans methyl iodide quaternary salt was prepared according to the process in 41 product is a strongly hygroscopic white Analysis for Pound procedure of Example 41 epeated by ducing 15 g of lidine as described in Example titrimetric value trans e hydrochloride salt prepared in the same manner as described in Example 30 and purified by crystallization from for found 15 methyl and 15 g of trans were placed in a sealed tube filled with After standing two hours at room the tube was solid product was collected by washed with ethyl acetate and in for i 50 The of Example was repeated by reducing 13 g of piperidlne as described in titrimetric value trans hydrochloride salt was prepared in the same manner as described in and purified by from a solvent mixture of acetone and ethyl for insufficientOCRQuality

Claims (1)

1. CLAIMS of the formula is 0 or is amino or a lower alkoxy is a straight or branched alkyl radical containing at least 2 carbon phenyl lower phenylcycloalkyl lower or a hydroxy alkyl radical or when is be an is hydrogen or a straight or branched alkyl radical or a hydroxy lower alkyl or and together with the nitrogen to which they are a saturated heterocyclic Compounds according to Claim 1 having the general formula where and have the same meaning as in Claim and their acid addition Compounds according to Claim 1 having general formula where and have the same meaning as in Claim and their addition Compounds according to Claim 2 or as described herein with reference to the A process for the production of compounds of formula I in Claim X is which comprises reacting a compound of formula with an amine of the formula and have the same meaning as in Claim 1 and Z is methox or A process according to Claim wherein a halide is added to an amine in the presence of an acid agent at a temperature of from to and the reaction is performed while the reactants are maintained at a temperature of from to A process according to Claim 5 or wherein the reaction is carried out in the presence of A process according to Claim 5 or wherein the reaction is carried out in the presence of an organic solvent or solvent A process according to any of Claims 5 to wherein the reaction is carried out in the presence of a polar solvent or solvent mixture and the halide is reacted with an A process according to Claim wherein a lower alkyl ester of a acid is reacted with an amine an the presence of a polar solvent at a temperature of from to 3 i A process according to Claims 5 and wherein the reaction is carried out in a sealed A process the production of compounds of general formula I in Claim wherein X is and their acid addition which comprises reducing compounds of formula I wherein X is 0 lithium aluminium hydride in the presence of an solvent at a temperature of from to if converting the thus prepared compounds into the corresponding acid addition salts A process for the production of compounds of the formula I in Claim wherein X is and their acid addition which comprises reacting a phenylcyclopropane with an amine of formula wherein and Rg have the same meaning as in Claim in the presence of an organic solvent and of an acid binding agent if converting the compounds thus obtained with the corresponding acid addition A process for the production of compounds of formula I in Claim 1 wherein X is and their acid addition which comprises reacting compound of with a compound of formula in the presence of an acid binding wherein and g have the same meaning as in Claim 1 and Y is A process according to Claim wherein a com ound of the formul Y in hi i i8 an is used as a reactant and the reaction is performed at a temperature between and in the presence of an organic A process according to Claim or wherein the reaction carried out in the presence of a mixture of organic A process according to Claim wherein the reaction is carried out in a sealed tube at a temperature above A process for the production of quaternary salts of compounds according to Claim wherein such compounds are reacted with a halide Dated this 20th day of For insufficientOCRQuality