SE431085B - 3- (2-HYDROXY-4- (SUBSTITUTED) PHENYL) CYCLOAL CANONES AND -CYCLOAL CANODES AND CERTAIN DERIVATIVES THEREOF USED FOR PHARMACOLOGICAL AND MEDICAL ENDAMALS - Google Patents

Description

10 45 20 STAY CC) \ 0 CD L » CD L m. 2 broad spectrum and minimal side effects. The most commonly used the agents, namely the acetylsalicylic acid preparations, have no practicality value in severe pain and, as is well known, gives rise to various non desirable side effects. Other analgesics, such as d-propokifene, codeine and morphine pose a risk of addiction. It is consequently obvious that there is a need for improved and substantial effective analgesics.

U.S. Patent No. 5,576,887 (Publ. '1971-O4- 27) describes a series of 1- (4'-hydroxy) alkyl-2-o-hydroxyphenyl- cyclohexane or compounds, which serve as intermediates for the preparation of 6,6-dialkyltetrahydro- and hexahydrodibenzo ¿B} g] pyranes useful as CNS depressants.

Summary of the Invention: It has now been found that certain cycloalkanones, cycloalkanols and unsaturated analogues thereof, which in the 5-position contains a 2-hydroxy-4- (substituted) ~ phenyl group of the formula I given below are effective as CNS agents, in particular analgesics, tranquilizers, sedatives and anxiolytics, and / or as anticonvulsants, diuretics and antidiarrheals for use in the treatment of mammals including people. Various derivatives also fall within the scope of the invention said compounds, which are useful in dosage form of compounds procedures for the preparation of the compounds as well as also intermediates useful in these processes. Association- The formulas in question have the following formula: . ? Rl “Kill _ z-w - where R is selected from a group consisting of saturated and unsaturated cycloalkyl groups selected from the group consisting of A B Q ' Rz Rs “R4 R RB 2 I-A (A, B separately) I-B II-A (A, B together form a group) c II-B 10 15 25 50 7809060-2 I-D II-D I-C (A, B separately) II-C (A, B together form a group) in which formulas the dashed lines represent a possible double bonding at one of the indicated sites, in which case R; not included in the formula; A is hydrogen and B is hydroxyl, hydroxymethyl or alkanoyl- oxy having 1-5 carbon atoms in formula I-A, i.e. when each of A and B represents an individual group; A and B in formula II-A, i.e. when A and B together form a group, also represents methylene or alkylenedioxy of 2-4 carbon atoms; Rq is selected from the group consisting of hydrogen, alkanoyloxy with 1-5 carbon atoms, benzyl, -P (O) (OH) 2 and mono- and disodium- and potassium salts thereof, -CO (CH2) 2COOH and sodium and potassium salts thereof, and -CO- (CH 2) p -NR 5 R 6, where p is an integer 1-4; where and one of R 5 and R 6 represents a hydrogen atom or an alkyl group with 1-4 carbon atoms or together with the nitrogen atom at which they are bonded, forming a 5- or 6-membered heterocyclic ring, namely piperidino, pyrrolo, pyrrolidino, morpholino or N-alkyl- piperazino having 1-4 carbon atoms in the alkyl group; R 2 is selected from the group consisting of hydrogen, alkyl of 1-6 carbon atoms, alkenyl having 5-6 carbon atoms, phenyl and phenylalkyl having 1-4 carbon atoms in the alkyl moiety; R 3 is selected from the group consisting of hydrogen and methyl; R 4 is selected from the group consisting of hydrogen and alkyl of 1-6 carbon atoms, wherein R 4 is hydrogen if R 5 is methyl; Z is selected from the group consisting of (a) alkylene having 1-15 carbon atoms; (b) - (alk4) m-O- (alk2) n- where each of (alkq) and (alkz) is alkylene having 1-15 carbon atoms, the sum of the carbon atoms in (alkq) and (alka) is at most 15; each of m and n is 0 or 1; and W is selected from the group consisting of hydrogen, pyridyl, - @ - W ,, where Wq is selected from a group consisting of hydrogen, fluorine and chlorine. 10 45 20 so 35 40 78Û906G-2 4 The dashed lines in formulas IA-ID evenly represent double bindings in the places mentioned.

Also within the scope of the invention are pharmaceutically acceptable acid addition salts of the compounds of formula I containing an alkaline group. Typical such compounds are those in which W enter pyridyl and / or OR4 represents a basic ester group.

In compounds with two basic groups, of course, addition salts of polybasic acids possible. Representative examples of such pharmaceutically acceptable acid addition salts are mineral acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate; salts of organic acids such as citrate, acetate, sulfosalicylate, tartrate, glycolate, malate, malonate, maleate, pamoate, salicylate, stearate, phthalate, succinate, gluconate, 2-hydroxy-5-naphthoate, lactate, mandelate and methanesulfonate.

Compounds of formulas IA-ID in which A and B together forms an oxo group and Rq is hydrogen; present in solution in equilibrium with their hemiketal forms. The keto and hemiketal forms of said compounds of formula I also fall within the scope of the invention.

When A is hydrogen and B is hydroxyl in the compounds of the formulas IA-In contains the compounds asymmetric centers in cycloalkyl the part in positions 1, 5 and 4 and when the cycloalkyl group is 6-8-joint, also in the 5-position, and they can of course include maintain additional asymmetric centers in the substituents. 4 and 5 and in the substituent -Z-W on the phenyl ring. Gis- ratio of the substituents in the 1-position on the cycloalkyl- the moiety and the optionally substituted phenol substituent in 5- the position is favored, and the trans ratio between 5- and 4-substi- and the 4- and 5-substituents on the cycloalkyl moiety are favored due to the (quantitatively) greater biological activity. Of for the same reason, the trans-5.4 ratio is also favored in the compounds with the formulas IA-ID, in which A and B together represent oxo. IN For simplicity, the above formulas represent them the racemic compounds, but they also include the racemic modi- the compounds of the compounds of the invention, the diastereomers the mixtures, the pure enantiomers and the diastereomers thereof.

The similarities of racemic mixtures, diastereomeric mixtures as well as the usefulness of pure enantiomers and diastereomers determined by the biological evaluation procedures described below. procedures. 10 45 5 7s09o6ø-2 In addition to the compounds of the above formulas fall within the scope of the invention various intermediates useful for position of the compounds of formula I. The intermediates have the following formulas: q (nnç _ on ° (IV) O 0 Q z-w Y @> <1 H2 - (cís ~ och trans isomers) (in which the stereochemical conditions are not stated) (II) 3 in which formulas Z, W, R 2 and R 5 have the meanings given above; Y is selected from the group consisting of eyano and formyl; t is an integer 4 ~ 8; R? is selected from the group consisting of hydrogen and alkyl of 1-4 carbon atoms; and - Q is selected from the group consisting of -CH 2 -, - CH 2 -CH (R 4) -, -CH 2 -CH 2 -CH (R 4) - and -CH 2 -CH 2 -CH 2 -CH- (R 4) -.

The compounds of formula IV represent hemiketal and the ketal forms of the saturated cycloalkyl compounds of the formula I (A-D) where A and B together represent oxo.

Due to higher biological activity compared to other compounds described herein benefit those compounds IA-ID, i which A and B together represent oxo; A ooh B represent- hydrogen and hydroxyl, respectively; R 2 is hydrogen or alkyl; R4 hydrogen or alkanoyl; R 5 is hydrogen or methyl; R 4 is hydrogen or alkyl; and Z and W have the meanings given in the following table: Z m _n_ W alkylene with 1-14 carbon- - ~ H atoms aikyien with 4-7 koi- - - @ -w, l, pyriayl atoms (anWm-o- (alkån o 4 - © -w, 1, pyriuyl O 1 H (alk¶) m-O- (alk2) n U-2 7809b tu! 6 Preferred compounds of formula I and especially those the saturated cycloalkyl compounds of formula I are those favored the associations in which: - each of R 4 and R 8 is hydrogen; Z is -O (cH5) 2 (cH2) 6 and W is hydrogen; Z is C 4-7 alkylene and W is phenyl; Z is -O-alkylene having 7-9 carbon atoms and W is hydrogen; Z is -O-alkylene having 4-5 carbon atoms and W- is phenyl; 'A is hydrogen and B is hydroxy (cis and transformer); A and B together are oxo; R 2 is hydrogen, methyl, propyl or propenyl; R; is hydrogen; and R 4 is hydrogen or methyl.

Particularly preferred are the saturated cycloalkyl compounds Of formulas IB and IC, wherein R 4, R 2, R 5, R 4, Z and W have them meanings as defined above for the preferred compounds and A and B represent hydrogen and hydroxyl, respectively.

Due to analgesic activity is also a specific preferred group the above-mentioned preferred compounds in which H 2 is methyl, propyl or propenyl and each of R 5 and R 4 hydrogen. 7 _ Detailed Description of the Invention: The saturated cyclo- the alkyl compounds of the invention falling under formula I, in which R 1 is hydrogen, is prepared from the appropriate 2-bromo-5- (Z-W substituent). Phenol by a series of reactions comprising first step protection of the phenol group. Appropriate protection groups are those that do not interferes with the following reactions and can be removed under during which there are no inappropriate reactions elsewhere in said compounds or products derived therefrom are caused. Representative such protecting groups are methyl, ethyl, benzyl or substituted benzyl, wherein the substituent is, for example, alkyl with 1-4 carbon atoms halogen (Cl, Br, F, I) and alkoxy with 1-4 carbon atoms. Protective or blocking ether groups can be removed using hydrobromic acid in acetic acid or 48% aqueous 55 containing hydrobromic acid. The reaction is terminated at elevated temperature and preferably at the reflux temperature. When Z is - (alk1) m-O- (alk2) n-, however, one must use such acids as polyphosphorus acid or trifluoroacetic acid.to avoid cleavage of ether the bond. Other reagents, such as hydroiodic acid, pyridine hydrochloride Chloride or hydrobromide can be used to remove protective 40 15 50 -55 40 7809060-2 ether groups such as methyl or ethyl groups. When the protection groups are benzyl or substituted benzyl groups they can be removed by catalytic hydrogenolysis. Suitable catalysts are palladium or platinum, especially on carbon. Alternatively, they can be removed by solvolysis using trifluoroacetic acid. Another method involves treatment with n-butyllithium in a gene against the reaction inert solvent at room temperature.

The exact chemical structure of the protecting group is not crucial importance of the invention, but of importance is its ability to operate in the manner indicated above. The person skilled in the art in question here industrial area can easily select and identify appropriate protection groups. Suitability and efficiency of a group such as hydroxyl protective group is determined by using the group in question in the reaction sequences set forth above. It should consequently be a group that is easy to remove in and for regeneration of the hydroxyl groups. Methyl and benzyl are preferred as protecting groups since they are easily removed.

The protected 2-bromo-5- (Z-W-substituted) phenol is reacted then partly with magnesium in a reaction-inert solution. agents and generally in the presence of a promoter, for example a copper (I) salt, such as copper chloride, bromide or iodide (for the benefit of 1,4-addition), partly with a suitable 4-R 2 -2-cyclo- alken-4-one (for example H-1fecyclohexen-1-one). Suitable for the reaction inert solvents are cyclic and acyclic ethers, for example tetrahydrofuran, dioxane and dimethyl ether of ethylene glycol (diglyme). The Grignard compound is formed in a known manner, e.g. by refluxing a mixture of proportion of the bromine component and two molar proportions of magnesium in a reaction-inert solvent, for example tetra- hydrofuran. The mixture thus obtained is then cooled to one temperature between about 0 ° C and about -20 ° C and the copper (I) iodide is added accompanied by the appropriate 2-cycloalken-1-one at a temperature between about 0 ° C and about -20 ° C. The amount of copper used (I) - Iodide is not crucial and can be varied widely borders. Molar proportions between about 0.2 and about 0.02 moles per molar bromine compound gives satisfactory yields of the cycloalkanone in which the phenolic hydroxyl group is protected (formulas IA- ID, Rq = a protecting group; R3 = H; A + B = oxo). ' The protected cycloalkanone is then treated with a suitable reagent for deprotection. The benzyl group conveniently removed in the manner indicated above. If the Protection Group is one 78Û9Û6J ~ e2 10 15 25 50 55 40 8 alkyl group (methyl or ethyl) it is removed by any of the the above procedures or by treatment with e.g. pyridine hydrochloride. When R2 is an alkenyl group, the cycloalkenes thus obtained serve as intermediates for the production of the corresponding ' the cycloalkenones (IA-ID) in which Ra is alkyl.

The cycloalkanol compounds of formula I are prepared from them protected the cycloalkanones by reduction. Sodium borohydride drawn as a reducing agent in this step, since one thereby does not only receives satisfactory yields of the desired product but also retains the protecting group on the phenolic hydroxyl group and in addition sodium borohydride reacts sufficiently long and with hydroxylic solvents (methanol, ethanol, water) for that they should be able to be used as solvents. Temperatures between about -40 ° C and about + 50 ° C is generally applied. lower temperatures, all the way down to about -70 ° C, can be applied for of the selectivity of the reduction. At higher temperatures reacts the sodium borohydride with the hydroxylic solvent. If higher temperatures desired or required for a given reduction are used was used as solvent is propyl alcohol or dimethyl ether of di- ethylene glycol. As a reducing agent, sodium tri- sec.-butyl borohydride, as this promotes stereoselective formation of trans-4,5-phenylcycloalkanol. The reduction is carried out in dry tetrahydrofuran at a temperature below about -50 ° C using of equimolar amounts of the ketone compound and the reducing agent.

Reducing agents such as lithium borohydride, diisobutyl aluminum hydride and lithium aluminum hydride can also be used but requires anhydrous conditions and non-hydroxyl solvents, such as 4,2-dimethoxyethane, tetrahydrofuran, diethyl ether and dimethyl ether ether of ethylene glycol.

The cycloalkanols of formula I, wherein A is hydrogen and each and one of B and OR 4 is hydroxyl can of course be obtained directly by catalytic reduction of the protected cycloalkanone over the palladium on carbon or by catalytic reduction or chemical reduction of the unprotected cycloalkanone (formula I, A + B = oxo, OR4 = OH) with use of the reducing agents described above.

In practice, it is preferred to produce the unprotected cyclones. the alkanols of formula I (A = H, B = ORq = OH) by reduction of the benzyl-protected cycloalkanones (formula I, A fi B = oxo, OR1 = benzyloxy) in the manner indicated above, since this enables stereo- 9 vsoaoeø-2 chemical control of the reduction and formation of cis-hydroxy- the epimer as the main product, whereby the separation and purification of the epimeric alcohols is facilitated.

The compounds of formulas IA-ID, in which the double bond 5 is in the 2,5-positions is prepared by Grignard reaction of the appropriate protected 2-bromo-5- (Z-W-substituted) phenol with a 5-alkoxy-2-cycloalken-4-one (having 1-4 carbon atoms in the alkoxy group) in a reaction-inert solvent at a temperature between about -50 ° C and about + 10 ° C. From the cyclone thus formed In the alkenone compound, the protecting groups are removed in the manner indicated above and the compound is reduced to the corresponding cycloalkenol.

Alternatively, the protected cycloalkanone is chemically reduced, e.g. pelvis using sodium borohydride, to the protected the cycloalkenol, from which protecting groups are then removed. For the regeneration of the phenolic hydroxyl group.

The compounds of formulas IA-ID, in which the double bonds is in the 5.4 position, is prepared from compounds of the formulas IA-ID, where A + B is oxo and the double bond is in the 2.5 position.

The process involves ketalization of an appropriate 2,5-unsaturated Compound falling into any of the formulas IA-ID, having a alkylene glycol having 2-4 carbon atoms in the presence of a dehydrating agents, for example p-toluenesulfonic acid, in such a solvent agents such as benzene, which allow azeotropic removal thereof as a by-product formed the water. Isomerization of the double bond To the 3,4-unsaturated ketal derivative takes place. Decetalization by mild acid treatment gives the 5.4-unsaturated compounds of formula IA-ID, where A + B represents oxo. By reduction of the oxo group in the manner indicated above, the corresponding alcohol is obtained.

The protected cycloalk-2-enones (formulas IA-ID, A + B = oxo, 50. Rq = protecting group) also serves as intermediates for compounds of formula I wherein R 5 is methyl. Introduction of the H5 substituent is obtained by conjugate addition of dimethyl copper lithium to it suitable cycloalk-2-enone. The process involves the reaction of the suitably protected cycloalkanone with dimethyl copper lithium i A reaction inert solvent, for example cyclic or acyclic ethers and in particular tetrahydrofuran at a temperature temperature between about 0 ° C and about -20 ° C. The organometallic the reactant produces 1,4-addition at the protected one the cycloalkanone to form a tertiary carbon atom. From that The H5-substituted protected cycloalkanone is then removed -a 40 '15 20 EO .55 40 Q IN J 4, - '\ 1 ~. 2 C 10 the protecting group and the alkanone are reduced or implemented first the reduction and then the removal of the protecting group on above. The 1,2-addition product is also obtained. in the compounds of formula IB, wherein the cycloalkyl moiety is saturated and En represents a substituent other than hydrogen, is prepared from suitable 2-bromo-5- (Z-W-substituted) phenol, in which the phenolic the group is suitably protected in the manner indicated above, by in the manner indicated above with magnesium to the Grignard compound.

This is then treated without insulation at reduced temperature, for example at a temperature between about + 40 ° C and about -20 ° C, with N, N-dimethylformamide. The temperature of the reaction mixture then rise to a value approximately corresponding to the spatial temperature and product, a protected 2-hydroxy-4- (Z-w-substituent) unerdated) benzaldehyde, is recovered in a known manner. The benzaldehyde derivative is then converted by the Wittig reaction with the appropriate 4-tri- phenylphosphoranylidene-2-alkanone in one reaction inert solvent at a temperature between room temperature and the reflux temperature of the solvent to a w- (2- hydroxy-4- (Z-W-substituted) phenyl) -5-alken-one. The above 2- propanone derivatives enable the formation of the cyclohexyl moiety. It saw the aryl alkenone formed is then reacted with a dialkyl malonate, preferably one in which the alkyl groups contain 1-4 carbon atoms, for cyclization of the alkenone. The reaction is carried out in one reaction-inert solvent, for example an alcohol with 4-4 carbon atoms, at a temperature between á one side about 25 ° C and on the other side the approximate solvent reflux temperature.

The carbalkoxy-substituted cycloalkanedione compound formed no one is then decarboxylated by treatment with an aqueous solution of sodium or potassium hydroxide at elevated temperature, for example at a temperature between about 50 ° C and about 100 ° C, and the cycloalkanedione derivative is isolated by per se known standard methods. It can then be ketalized by turnover with methanol or other alcohol having up to 4 carbon atoms or with an alkylene glycol having 2-4 carbon atoms in the presence of a dehydrogen ratifying agents, for example p-toluenesulfonic acid.

When it comes to the cyclohexyl derivative, it is then reacted The 5-methoxy-2-cyclohexene-1-one derivative with lithium aluminum hydride in a solvent inert to the reaction, for example di- g ethyl ether, dioxane, tetrahydrofuran or diglyme, at a temperature 40 15 20 25 50 55 40 fm 7809060-2 between about -10 ° C and about + 10 ° C and worked up with dilute mineral acid. The aryl-substituted 2-cyclohexene-4- thus obtained the ions are then treated with the appropriate dialkyl copper-lithium in a suitable reaction-inert solvent, for example hexane, diethyl ether or a mixture of these solvents cyclic ethers, such as tetrahydrofuran, at a temperature between about 0 ° C and about -20 ° C. From the protected The α (Z-W-substituted) -2-hydroxyphenylphysic-R4 cycloalkanone the protecting group is then removed and the compound is reduced, or the reduction is carried out first, after which the protection group removed, all in accordance with the procedures described above.

Alternatively, 5- [E-benzyloxy-4- (Z-W) -phenyl] -5- the alkoxy-2-cyclohexen-4-ones with the appropriate Grignard compound R4NgBr, whereupon the acid is obtained by acid hydrolysis The 5-β-benzyloxy-4- (Z-W) -phenyl7β-Ru-2-cyclohexen-1-ones, which catalytically reduced to the corresponding cyclohexanones.

By debenzylation in the manner indicated above, 5-¿É ¥ hydroxy- The 4- (Z-W) -phenyl7 ¥ 5-H4-cyclohexanones, which are then reduced on above to the corresponding cyclohexanols.

The compounds of formula IC wherein the cycloalkyl moiety is saturated and R 4 represents a substituent other than hydrogen prepared by ring expansion of the cyclohexyl derivative. The reaction between it suitable 5β-benzyloxy-4- (Z-W) -phenyl17β-R4-cyclohexanone and lithium dibromomethane in a reaction-inert solvent, for example diethyl ether, gives 1-dibromomethyl-5-β-benzyloxy-4- (Z-w) - phenyl7 ¥ 5 ~ R4-cyclohexanol. Additional turnover of a dibromo- methyl-cyclohexanol in a reaction-inert solution. agents, for example tetrahydrofuran, with n-butyllithium give 5-1É- hydroxy-4- (Z-W) -phenyl7-5-R4-cycloheptanones, from which after removes the protecting groups and submits to the associations reduction or you first carry out the reduction and remove then the protection groups, all in accordance with those described above procedures.

The compounds of formula ID, wherein the cycloalkyl moiety is saturated and Ru represents substituent other than hydrogen, is prepared by ring expansion of the cycloheptyl derivative according to the above described procedures. in When R4 is hydrogen in formulas IB-IC it is possible to in accordance with the procedures described above, expansion, so that the ring in question will contain one r: IN 10 45 50 v55 40 S () « 2-2 06 n 12 to methylene group, i.e. one obtains compounds of the formula IC and ID respectively.

The reactants 2-bromo-5- (Z-W-substituted) -phenol is prepared by bromination of the appropriate 5- (Z-W-substituted) phenol in accordance with standard procedures, for example by treatment with bromine in carbon tetrachloride at a temperature between about 20-50 ° C.

The necessary 5- (Z-W-substituted) phenols are prepared, if they are not known compounds, as described herein context, A convenient procedure for producing such reactants in which Z is alkylene or (alk4) m-O- (alk2) n- includes Wittig reaction with the appropriate aldehyde, e.g. vis 2- (5-hydroxyphenyl) -2-methyl-propionaldehyde, whose hydroxyl group protected by benzyl ether formation. Said aldehyde is then treated followed by the appropriate alkyltriphenylphosphonium bromide, the alkyl group of which extends the propionaldehyde group to the desired length. By one Typically, the aldehyde is added to a slurry of sodium dimsyl and alkyltriphenylphosphonium bromide in dimethylsulfoxide at a temperature below 50 ° C, for example between about 10-3050.

When the reaction is complete, the alkene-substituted, protected the phenol in a known manner. By hydrogenating the alkene over palladium-on-carbon, the desired 5- (Z-W-substituted) phenolic the island ether. Through well-thought-out choice of those as starting material use the compounds (5-hydroxyphenyls) -substituted aldehyde and alkyl-tri-phenylphosphonium bromide the necessary ones are obtained the reactants 3- (Z-W-substituted) phenol.

By preparing the appropriate 4-R2-2-cycloalken-1-one synthesis is possible in accordance with the above procedures of the compounds of formulas IA-ID, wherein R 4 is hydrogen. Through turnover the appropriate 4,3-cycloalkanedione with an alcohol having 1-4 carbon atoms and an acid catalyst, for example p-toluenesulfonic acid, in a reaction-inert solvent, for example benzene or toluene, and with an apparatus for water separation at temperatures at which the reaction solvent boils under reflux, 5-alkoxy-2-cycloalken-4-ones are obtained. Through the sale of 5-alkoxy-2-cycloalken-1-one with lithium iodisopropylamine in one reaction inert solvent, for example tetrahydro furan, in the presence of hexamethylphosphoramide and appropriate RQX, where X is bromide or iodide or any other suitable leaving group, 4-R2-3-alkoxy-2-cycloalken-1-ones are obtained. These are then traded after with lithium aluminum hydride in a reaction inert 10 45 20 25 50 35 40 7809060-2 45 solvent, for example diethyl ether, at a temperature between about -10 ° C and + 10 ° G and worked up with diluted mineral acid. Thus, the obtained 4-R, -2-cycloalken-1-one is converted thereafter in accordance with the procedures described above.

Compounds of formula IB-ID, wherein the cycloalkyl moiety is saturated and where each of R 2 and R 4 represents another substituent than hydrogen, is prepared by reacting the appropriate 5-1Ebenzyloxy-4- (Z-W) phenyl7α5-methoxy-2-cyclohexen-4-one with lithium iodisopropylamide in a reaction-inert solution low temperature, for example at a temperature between -50 ° C and -78 ° C. Hexamethylphosphoramide and suitable B2- iodide (where R 2 does not represent hydrogen) is then added for the preparation of a 5- [Albenzyloxy-4- (Z-W) -phenyl] ¥ 5- methoxy-6-R2-2-cyclohexen-1eon. Additional turnover of said compound with the appropriate Grignard compound R'4MgX (where R'4 is alkyl) under normal conditions for Grignard reaction gives a 5-ε-benzyloxy-4- (Z-W) phenylylu-R2-5-Rf4-5-cyclohexene- -1-on. By debenzylation and reduction of this compound in the manner described above, the desired 5-β-hydroxy-4- - (Z-W) -phenyl7A4-R2-5-R'4-cyclohexanol. By reducing the double bond in 5-olbenzyloxy-4- (Z-W) -phenyl7-4-R2-5-R'4- The -5-cyclohexen-4-one above Pd / C is obtained correspondingly, saturated cyclohexanone derivative. These latter derivatives serves as intermediates for the production of the equivalent cycloheptanone and cyclooctanone derivatives by ring expansion - in the manner indicated above.

A convenient process which enables selective alkylation of 5- (2,4-dihydroxyphenyl) cycloalkanones at 4-hydroxy the group comprises as a first step the conversion of 5- (2,4- dihydroxyphenyl) cycloalkanone to a ketal. The transformation achieved in a manner well known for ketalization, for example by reacting the 5- (2,4-dihydroxyphenyl) cycloalkanone with an alcohol, in particular an alcohol having 1-4 carbon atoms, i presence of an acid, for example sulfuric acid, p-toluenesulfonic acid acid, hydrochloric acid, under conditions for removal of the by-product formed the water. A favorable procedure includes reacting the 5- (2,4-dihydroxyphenyl) cycloalkanone with a orthoformic acid ester in an alcohol corresponding to the alcohol content of the orthoformic acid ester as solvent. Trimethyl orthoformate and methanol are suitable reactants together <1 OD \ .Q C) .J \ 10 20 EO u: \. "| 40 0-2 44 with concentrated sulfuric acid, anhydrous HCl or ammoniumf chloride as catalyst.

The ketal thus formed is then alkylated by reaction. with a suitable alkylating agent, for example W-Z-X, where W and Z have the meanings given above and X is selected from one group consisting of chlorine, bromine, mesyloxy (CH5 ~ SO2-0) and tosyloxy (p-CH5-C6H4-SO2-O-) in the presence of an acid acceptor, for example sodium or potassium carbonate. The alkylated the ketal is then decetalized according to known procedures by treatment with an aqueous acid.

Another process for the preparation of 5- (Z-W sub- substituted) phenols, 'where Z is alkylene or (alk1) -O- (alk2) n- involves Wittig reaction with a suitable phenolic aldehyde or ketone, for example 5-hydroxybenzaldehyde or a 5- (hydroxyphenyl) alkyl ketone in which the phenolic hydroxyl the group is protected, for example, by conversion to benzyl, methyl or ethyl ether. By selecting suitable reaction comf components can be prepared with straight or compound compounds. branched alkylene groups (Z). When a ketone, for example 5- hydroxyacetophenone, used as a reactant is obtained compounds in which Z has a methyl group on the adjacent carbon atom the phenyl group.

Substitution of one methyl or ethyl group on others places; for example on the β-carbon atom of the alkylene group, is obtained by selecting the appropriate carboalkoxy-alkylidene-triphenyl- phosphorus, for example (C 6 H 5) 5 P = C (R ') - COOCEHS. It so formed unsaturated ester is reduced to the corresponding alcohol by reaction with lithium aluminum hydride. Alternatively the alcohol is produced by catalytic reduction thereof unsaturated ester using palladium-carbon, when -phenolic protecting group is other than benzyl (for example methyl), whereupon the saturated ester thus formed is treated with lithium aluminum hydride. By conversion of the alcohol thus obtained to the corresponding tosylate or mesylate, subsequently alkylation of the tosylate or mesylate with an alkali metal salt of the appropriate reactant HO- (alkg) -W and finally removal of the protecting group, the desired 5- (Z-W- substituted) phenols.

A variant of the above sequence involves bromination of the alcohol instead of converting it to a tosylate 40 45 20 25 50 55 40 7809060-2 15 or mesylate. Phosphorus tribromide is a convenient brominating average. The bromo derivative is then reacted with the appropriate H0- (a1k2) - W in the presence of a suitable base (Williamson's ether synthesis).

The bromine compounds also serve as valuable intermediates products for extending the chain length in the alkyl part of the above sequence for the preparation of compounds in which Z is -alkylene-W. The process involves the treatment of bromine the derivative with triphenylphosphine to produce the corresponding triphenylphosphonium bromide. By reacting triphenylphosphonium the bromide with the appropriate aldehyde or ketone in the presence of a base, for example sodium hydride or n-butyllithium, one is obtained unsaturated derivative, which is then catalytically hydrogenated to it correspondingly saturated compound.

An alternative method of introducing an alkyl or aralkyl group in the aromatic nucleus and especially one group in which the carbon atom adjacent to the aromatic nucleus is one tertiary carbon atom, includes acid-catalyzed electrophilic aroma. ataic substitution of guaja carbon with a tertiary alcohol in presence of an acid, for example methanesulfonic acid. The general the process consists of reacting a mixture of methane sulfonic acid and equimolar amounts of guaiacol and tertiary alcohol hollow at a temperature between about 50-80 ° C, until the reaction is essentially complete. The product is insulated by pouring the reaction mixture onto ice, then extracting with a suitable solvent, for example methylene chloride, implemented. The 2-methoxy-4-alkylphenol formed is converted then to the desired 5-alkylphenol by removes the phenolic hydroxyl group. This procedure involves the conversion of the hydroxyl group to a dialkyl group. phosphate group by reaction with a dialkyl chlorophosphonate, for example diethyl chlorophosphonate, or with diethyl phosphonate and triethylamine. By treating the dialkyl phosphate with lithium / ammonia and subsequent demethylation of the one thus obtained alkylated methyl ether with boron tribromide or pyridine hydrochloride chloride or with another known demethylating agent it is obtained desired 5-alkylphenol.

A convenient process for the preparation of compounds according to the invention in which -Z-W is -O- (alk2) n-W comprises use of 4-bromoresorcinol as starting material. Procedure it includes protection of the two hydroxyl groups in the resorcinol V) 10 45 20 25 §O 55 40 1D Û \ CD PO ~ 16 by benzylation according to the standard method. The benzyl group preferred as a protection group in this procedure, since it can be easily removed by catalytic hydrogenation without cleavage. formation of the ether group -O- (a1k2) n-W. Other protection groups, for example alkyl (such as methyl or ethyl) can of course, can also be used, but the benzyl group is preferred where it gives gives rise to fewer side reactions. The protected 4-brake travel the quinol is then subjected to Grignard reaction and reacted with the appropriate cycloalkenone in a reaction inert solvent in the manner described above. The 5- (2,4- the dibenzyloxyphenylo-cycloalkanone is then subjected to lytic hydrogenation over palladium-on-carbon, thereby obtaining the corresponding 5- (2,4-dihydroxyphenyl) -cycloalkanone which occurs in equilibrium with its hemiketal. Hemiketalen om- is then converted to the corresponding alkyl ketal of 1-4 carbon atoms in the alkyl moiety, for example methyl ketal by reaction with, for example, a trialkyl orthoformate, for example trimethyl orthoformate in a suitable solvent, for example an alcohol having 4-4 carbon atoms, for example methanol, in the presence of concentrated sulfuric acid. The alkyl ketane thus formed then cooled with the appropriate alkyl or aralkyl methanesul- phonate or tosylate in the presence of anhydrous sodium or potassium carbonate in a suitable reaction inert solvent, such as N, N-dimethylformamide, at a temperature between about 75-400 ° C. This method has the advantage of enabling use of simpler compounds throughout the reaction the sequence. The O-alkylated or aralkylated ketal de- then ketalized by reaction with, for example, acid to prepare the corresponding 5- (2-hydroxy-4- [Ö- (alk2) n7phenyl) cycloalkanone, which occurs in equilibrium with its hemiketal.

Since the compounds of formulas IA-ID, wherein A and B together represent oxen and R4 hydrogen, occur in solution in equilibrium with the hemiketal form and some, in crystalline linear condition, occurs substantially completely in the hemiketal form, is included within the scope of the compounds with formulas IA-ID, where A and B together represent oxo and R4 is hydrogen, both the hemiketal and keto forms.

The compounds of the present invention in which A and B together represent methylene is readily prepared from 40 45 20 25 §O 55 40 ~ 7809060-2 47 the corresponding oxo compounds by the Wittig reaction with methylenetriphenylphosphorane or other suitable methylide. The usual procedure involves the preparation of Wittig- reagents, i.e. methylidene, in situ and immediately thereafter preparation of the methylidene and reaction thereof with suitable oxo compound. A convenient process for producing the methylidene involves the reaction of sodium hydride with dimethyl sulfoxide (sodium dimsyl) at a temperature between about 50-80 ° C, usually until the hydrogen evolution subsides, whereupon reacting the solution of methylsulfinylcarbonane thus obtained ion (dimsyl) with, for example, methyltriphenylphosphosium bromide at a temperature between about 40-80 ° C. To the so formed the solution of the ylide compound is then added to the appropriate oxo- the compound and the mixture are stirred at a temperature between room temperature and about 80 ° C. The methylene compound thus formed the insulation is insulated in a known manner. Hydroboration-oxidation of the methylene compound then gives the hydroxymethyl derivative such as exemplified in the present context. Boron in the hydrohydro- furan is preferred for the hydroboration step, since it is commercially available and gives satisfactory results desired hydroxymethyl compound. The reaction is carried out in in tetrahydrofuran or diethylene glycol dimethyl ether (diglym). The borane product is not isolated but oxidized directly with alkaline hydrogen peroxide to the hydroxymethyl compound.

Other processes for the preparation of the methylidene are known and can be applied instead of the above written procedure. Typical procedures are described by Maercker and Organic Reactions, 44, 270 (1965). In oxo compound with the formulas IA-ID, you can, if you wish, protect the phenolic hydroxyl group, for example by conversion to an alkanoyloxide derivative. Other protection groups may, of course, be used. The hydroxyl group can be converted to ethers, thus as tetrahydropyranyl ethers. However, it is not absolute necessary to protect the phenolic hydroxyl group, if a sufficient base is present to convert it phenolic hydroxyl group to an alkoxide.

Esters of the compounds of formulas IA-ID, wherein Rq is alkanoyl or -CO-QCH 2) pNR 5 R 6 is readily prepared by reacting compounds of formulas IA-ID, wherein R 4 is hydrogen, with the appropriate alkanoic acid or acid of the formula vsoeøeß-2 5 qß 40 45 20 25 ' 50 55 40 HOOC- (CH2) PNR $ R6 in the presence of a condensing agent, for example dicyclohexylcarbodiimide. Alternatively produced by reacting a compound of formula IA-ID with suitable alkanoic acid chloride or anhydride, for example acetyl- chloride or acetic anhydride, in the presence of a base, e.g. pelvis pyridine.

Esters of compounds of formula IA-ID where A is hydrogen and B is hydroxyl or hydroxymethyl and OR, is hydroxyl is prepared by acylation in accordance with those described above procedures. Compounds in which only R (R = OH, CHEOH) is acylated is obtained by mild hydrolysis of the corresponding diacyl derivatives, taking advantage of it the phenolic acyl group is more easily hydrolyzed. They so formed_ the compounds can then be further acylated with various acylating agent for the preparation of a difester ester compound with different ester groups. _ The analgesic properties of the compounds of the invention properties have been determined by sampling using nociceptive stimulus.

Tests using thermal nociceptive stimulus a) Analgesic test with mouse on hot plate The applied method is modified after Woolfe and MacDonald, J. Pharmacol. Exp, Ther., 80, 500-507 (1944). One regulated heat stimulus was applied to the paws of mice on a 0.5 cm thick aluminum plate. A 250 watt IR lamp with reflector was placed under the lower surface of the aluminum plate. One temperature controller connected to electrical resistance thermometers meters on the upper surface of the plate controlled the lamp so that the temperature kept constant at 57 ° C. Each of the experimental animals was was immersed in a glass cylinder standing on the hot plate with diameter 16.5 cm and the time was measured from the moment of the animal 'paws touched the plate. The experimental animals were observed 0.5 and 2 hours after treatment with the test compound with respect to Ûe first SVaS8 movements in one or both hind paws or until 40 seconds have elapsed without such movements. Morphine has MPEBO = 4 '5.6 Elg / kg (S.C.). b) Analgesic test with tail movement in mice The tail movement test on mice is modified after D'Amour and Smith, J. Pharmacol. Exp. Ther., 72, 74-79 (1941) med use of regulated, high-intensity tail heating. 10 20 25 50 u: \; 1 78090 0-2 1 .; 19 Each of the experimental animals was placed in a well-enclosed manner metal cylinder with the tail protruding at one of the cylinders End. The cylinder was arranged so that the tail lay flat over one shielded heat lamp. At the start of the test, one was shifted over the lamp existing aluminum plate so that the light beam could pass through a slit and focus on the end of the tail. Sam- an early stop was started. The reaction time of a sudden movement of the tail was determined. Untreated mice respond usually within 5-4 seconds after exposure to the lamp.

The end point for protection is 10 seconds. Each experimental animal were tested 0.5 and 2 hours after morphine treatment and with the test association. Morphine has MTEBO 5.2-5.6 mg / kg (s.c.). c) Try dipping the tail in a water bath The process is a modification of the container process developed by Benbasset and co-workers, Arch. int.

Pharmacodyn., 122, 454 (1959). Albina male mice with body weight 19-21 g (Charles River CD-1) were weighed and marked for identification. tification. Five experimental animals were normally used in each treatment group with each experimental animal serving as its own control.

For a general Utsållnínë, new test compounds were first administered 56 mg / kg intraperitoneally or subcutaneously in a volume about 10 ml / kg. Before treatment and 0.5 and 2 hours thereafter 'each of the experimental animals was placed in a cylinder. Each cylinder was fitted with holes for adequate ventilation and closed with a round nylon plug, through which the experimental animal tail stuck out. The cylinder was held in an upright position and the tail completely immersed in a constant temperature water bath 56 ° C. The end point of each attempt is an energetic jerk or spasm in the tail coupled with a motor response. In some if so, the endpoint may be less severe after treatment. For to prevent unnecessary tissue damage, the sample and tail were terminated was taken out of the water bath within 10 seconds. The reaction time for response in seconds was recorded with a tolerance of 0.5 seconds.

A vehicle control and a known standard were tested at the same time the screening of the experimental animals. About the test association's activity did not return to baseline in the test after 2 hours the reaction time was determined at 4 and 6 hours. Final determination was carried out after 24 hours in cases where activity was still was observed at the end of the test day. 10 45 20 25 50 55 20 Tests using chemical nociceptive stimulus Suppression of that of phenylbenzoquinone as an irritant induced convulsion Groups of five mice each (Carworth Farms CF-1) treated subcutaneously or orally with saline, morphine, codeine or the test compound. 20 minutes (in case of subcutaneous istration) or 50 minutes (for oral administration) later the experimental animals in each group were treated by intraperitoneal injection of phenylbenzoquinone, a known irritant that it causes abdominal contractions. The experimental animals observed was observed with respect to the presence or absence of convulsion for 5 minutes starting 5 minutes after the injection of medlet. MEEO for the pretreated animals with respect to blockade of convulsion was determined. 5 Test using pressure-induced nociceptive stimulus Effect of Haffner's method of pinching the tail A modification of Haffner's method, Experimental Examination Painkiller. Deutsch. With. Wschr., 55, 751-752 (1929) was applied to determine the effect of the test compound on aggressive attack response elicited by pinching the tail.

'Albina male rats weighing 50-60 g (Charles River, Sprague-Dawley CD) was used as a test animal. Before treatment and again 0.5; 4; 2 and 5 hours later attached to the tail root a clamp (Johns Hopkins 2.5-inch "bulldog" clamp).

The end point of each experiment was marked with clearly stated attack and bite against the bothersome stimulus and reaction time for the attack was determined in seconds and recorded. The clamp was removed after 50 seconds, if attack then not yet occurred, and the response time for response was recorded as 50 seconds.

Nbrfin is active at 47.8 mg / kg (i.p.).

Test using electrical nociceptive stimulus The "Flinch-Jump" test A modification of the method according to Tenen, Psychopharma- cologia, 12, 278-285 (1968) in which the experimental animal jerks to of pain, was used to determine the pain threshold.

'A1bino rats, males 475-200 g (Charles River, 10 hrs.) Ul 50 ) 7809I ': ~ C * -, __ l n 21 Sprague-Dawley CD) was used for the experiment. Before the experimental animals obtained the compound was dipped each of the paws in a 20% glycerol / saline. The animals were then placed in a chamber and the paws were subjected to a series of shocks of 1 second each with increasing intensity and at intervals of 50 seconds. These intensities were 0.26; 0.59; 0.52; 0.78; 1.05; 1.51; 1.58; 1.86; 2.15; 2.42; 2.72 and 5.04 mA. Behavior of each laboratory animal was assessed with respect to the presence of (a) twitches, (b) beeps and (c) jump or rapid forward movement at the insertion of the shock.

Each experimental animal was exposed to a single series of shocks increasing intensity just before and 0.5; 2; 4 and 24 hours after treatment with the agent.

The results of these tests were recorded as the largest percent possible effect (% WEE). % MPE for each group was compared statistically % MPE for the standard used and for the values held before treatment with the association. % HEE is calculated with the following formula: Gd fi ï - control time - control time test time break time X 100 For oral or parenteral administration of the compound the compounds of the invention for use as analgesic agents. they are conveniently administered in the form of mixtures. Such mixtures contains a pharmaceutical carrier selected with respect to method of administration and standard pharmaceutical practice. Thus the compounds may be administered in the form of tablets, pills, powders or granules containing excipients such as starch, milk sugar, certain types of clay, etc. They can be administered in capsules, in admixture with the said or equivalent ' excipients. They can also be administered in the form of oral suspensions. ions, solutions, emulsions, elixirs and syrups, which can contain flavors and colors. For oral administration of it the therapeutic agents of the present invention are for most applications suitably with tablets or capsules containing between about 0.01 and about 100 mg. the doctor determines the dose that is most suitable for one patient, and this dose varies with the patient's age, body weight and sensitivity as well as with the mode of administration. IN In general, however, the initial analgesic dose for Adults vary between about 0.1 and about 750 mg per day in in the form of a single dose or divided into sub-doses. In many cases 9 40 15 20 55 22 it is not necessary to administer more than 400 mg per day. The favorable dose is between about 4.0 and about 500 mg / day and the preferred dose is between about 4.0 and about 50 mg / day. Gynn- The co-parenteral dose is between about 0.4 and about 400 mg / day and the preferred dose is between about 0.4 and about 20 mg / day.

According to the invention, it is furthermore intended that pharmaceutical preparations ningar, i.a. unit doses, valuable when using the the compounds described herein as analgesics and in other written use. The dosage can be as indicated above, by administered in a single dose or in multiple doses to obtain the daily dose that is effective for a particular purpose.

The compounds described in the present context may prepared for oral or parenteral administration in solid form or liquid form. Capsules containing the compounds according to - the invention is prepared by mixing together a part by weight of the compound with 9 parts by weight of excipient, for example starch or milk sugar, after which the mixture is introduced into collapsible gelatin capsules, so that each capsule contains 400 parts of the mixture. Tablets containing said compounds are prepared by processing appropriate mixtures of compounds none and standard ingredients used in manufacture of tablets, such as starch, binders and lubricants, so that each tablet contains between 0.40 and 400 mg of the purification per tablet.

Suspensions and solutions of the compounds according to the invention, in particular those in which Rq in formulas I and II represents hydroxyl, is often prepared just before use. to avoid problems with the suspension or the stability of the solution, for example precipitation of _ningen during storage. Mixtures suitable for this purpose are usually dry and solid and reconstituted to be able to injected.

Several of the compounds of the present invention have tested for analgesic activity using the procedures described above. The associations have the following formula: 'IO 7809060-2 25 The compound with which they are listed in Table I. the results obtained have the above formula, in which A represents H and B represents OH. The results in table II has been obtained with compounds of the same formula, in which A + B, however, represents oxo.

The following abbreviations were used in the tables: PBQ = phenylbenzoquinone induced convulsion; TF = jerking i the tail; HP = hot plate; ETC = straight tail clamp and FJ = jerk.

The individual values in the tables are values for ED5O.

A number followed by a second number in parentheses indicates the percentage protection observed at a given dose. Thus, 5'l (56) 54% protection at a dose of 56 mg / kg body weight. nl ..

... HL / C now 0 ,. 00 24 vmw m @ ^ Nmovw ^ mmovo m mmofmnmnp monm fl oí mm w mmwo Ämmovo m m moè fl o mm M mmwo Ãmmovø m m moàän » m.o m @ ^ ~ movN ^ mmovo m mmolmnmnp moxmqwnp nwmvwm m w ^ mmuvm ^ mmovo m m mo | mqw ~ » Awmvßm m @ ^ mmøVN ^ mmovo m m mo | w fl ° ß.ß m, m ovvmm Aovvßm m.v m @ ^ mmovm ^ mmovo m m. mø | wH0_ @ .m #, m ^ ovVmw ^ @ v mm mmwo m ^ Nmov ^ mmovmoo m m molm fl o Awmvwm mmwo mñmmovñmmovmoo m m mouwnmnp wmhm m w ^ mmovm ^ mmovo mmo | mqmnp m moum fi o w.m m m ^ mmovm ^ mmoVo m m monmqmnp ß. @ o, fl w »@ v, v m w ^ ~ movN ^ mmovo m _ m molm fi o osm .hm ha mm. amm 3 N mm Nm m »Ho fl umnuw flflfl ëwm .o.m Åmvïmëv øuhxn R .Hm flfi w ~ wx \ wav ommm »@@ fi> fl @ xm xm fl @ wmHmq <" H H fi wpma KIrvvvvNNOOVVVV ' p .. ff) - ñ / fl / mx \ mE on EO wow Gm flfi> .b fi ßxm flfi u .v fl š fl nwu fi wuwv fi uhuw fl Aøv .wo fl m fl mllq Aob .mmßhmlmo Mw flfl o fl ww> m .Hmpw fi hwwmß Amv vm.v w ^ mmuvw ^ mmovo m mmo | w fi o o v mwmvmà O m H AUVO .x 83mm w 1 m m O m w Q v #. @ w.ov ^ ovvwm Aov Åwmwmf w ^ mmov ^ movo m m Q o vmm mv m ^ movm ^ mwøVv m m 0 m Awmvom w ^ mmovm ^ mmovo Apv m 0 v wm fl m m ^ mmov ^ mmuvmuo m m o v Awmvom w ^ mmovm ^ mmovo m m o m v , Awmvvm w ^ mmuvN ^ mmoVo mmm m Ü A vv . m mv m. @ w ^ mmovm ^ mmuV @ m m O v oam hm ma mm æmm N fl m mm oxo x ¶M + < fl o fi wmHäm flflfi âñm .Ulm .mmäïw fi v Uükgm ä. .Ho fifi w ^ mx \ msV omam »w @ fi> fl pxm Mw fi pmmHmm <“ HH fifl wßma * Q CD .Q (IN: 10 šO 40 (ÅK ~ U ': \.' \ 26 The activity of the compounds according to the invention as diuretics determined by the procedure of Iipschitz and co-workers, J. Fharmacol., 197, 97 (1943) in which rats are used as experimental animals. The dosage for this use is the same as stated above regarding the use of the compounds as analgesics.

The usefulness as antidiarrheal was determined by a modification of the procedure according to Neimegeers and co-workers, Modern Pharmaoology-Toxicology, Willem van Bever and Harbans Ial, Eds., 7, 68-75 (1976). Rats with body weight 470-200 g (Charles_River CD-1) was housed in group cages 48 hours before the test.

The animals were fasted all night with water available ad libitum before administration of castor oil. The test compound was administered subcutaneously or orally with a constant volume of 5 ml / kg body weight in a 9.4 ethanol, 5% Ermirnon ELæo (a polyoxyethylated vegetate » essential oil as an emulsifier from Antara Chemicals, New York, N.Y.) 5 and 90% saline as a vehicle followed one hour later by an oral administration of 4 ml of castor oil. The experimental animals were placed lined up in small individual cages (20.5 X 16 X 21 cm) with suspended wire mesh as a floor, under which replaceable cardboard sheets are placed des. These carton disks were inspected 1 hour after castor oil the administration with regard to the presence or absence of diarrhea. A control group was used for each day's test group treated with vehicle / castor oil. The results were recorded as the number of laboratory animals protected 1 hour after administration of castor oil. In general, the dose levels correspond to use of these compounds as the antidiarrheal levels at their use as analgesics.

The tranquilizing activity of the compounds according to the invention was determined by oral administration to rats in doses from about 0.01 to about 50 mg / kg body weight and observed vation of subsequent decrease in spontaneous motor activity.

The daily dose for mammals is between about 0.04 and about 400 ml.

The anticonvulsant activity was determined by subcutaneous administration of the test compound in male mice (Swiss Charles River) with a body weight of 44-25_g in a vehicle of the type indicated was used to determine the utility of the compounds as antidiarrhosis. The experimental animals were used in groups of each five mice. The day before use, the mice were fasted whole \, "| 45 55 HO night with water available ad lib. With hypodermic needle No. 25, 40 ml / kg body weight was injected. The animals were treated with the test compound and one hour thereafter transcorneally with electroconvulsive shock 50 mA and 60 Hz. At the same time control samples were taken, only the vehicle was injected. In the case of convulsive shock treatment, persistent stretching muscle contractions occurred vulsions in all control animals with a reaction time of 1.5 5 seconds. Protection was recorded when a laboratory animal was not showed persistent stretching muscle convulsions for 40 seconds after the administration of the electroconvulsive shock.

Anxiolytic activity was determined in the same manner as convulsion activity, but pentylene was used as an irritant. tetrazole administered intraperitoneally at 120 mg / kg.

This treatment causes clonic muscle cramps in less than one minute for more than 95% of the control mice treated. Protection was noted when the reaction time to convulsion was delayed to at least double when pretreated with an anxiolytic average.

Sedative / depressive activity was determined by treatment of a group of 6 mice subcutaneously with different doses of test compounds ingarna. 50 and 60 minutes after the treatment, the mice were placed on a rotating rod where they were left for 4 minutes and their teende was assessed. Inability to stay on the rod is considered as a sign of sedative / depressive activity.

Example 4: 5-12-Benzyloxy-4- (1,4-dimethylheptyl) -phenyl] cyclohexanone A solution of 75.0 g (0.195 mol) of 2- (5-benzyloxy-4-bromo- phenyl) -2-methyloctane in 200 ml of tetrahydrofuran was added slowly to 9.25 g (0.586 mol) of magnesium metal powder with particulate size 0.177-0.240 mm. The mixture thus obtained was boiled under reflux for 20 minutes and then cooled to -18 ° C.

Copper (I) iodide (1.84 U; 9.7 mmol) was added and stirred continued for 10 minutes. To the mixture thus obtained was slowly added a solution of 48.5 g (0.195 mol) of 2-cyclohexene 4-one in 40 ml of tetrahydrofuran at such a rate that the reaction the temperature was kept below -5 ° C while cooling in an ice bath and salt. The reaction mixture was stirred for an additional 50 minutes. . at a temperature below 0 ° C and then set at 500 ml of 2N-HCl and 2 l of ice water, thus stopping the reaction.

The reaction mixture was extracted with ether (5 x 500 ml). The vsosoeu-2 28 40 45 20 ' 25 STAY 55 ' the combined extracts were washed with water (2 x 400 ml), with a saturated sodium chloride solution (2 x 400 ml), dried over magnesium sulfate and evaporated to an oil. This was purified by column chromatography on 4.6 kg of silica gel and elution was performed with 20% ether-cyclohexane to give 62.5 g (yield 79.7%) of the product as an oil.

IR: (CHCl 3) 1709, 1615 and 1575 cm -1.

Ms: m / 6 406 (M +), 562, 521, 515 and 91.

The compounds listed below were prepared on above from suitable 2-benzyloxy-4-Z-W bromobenzenes and suitable cycloalkenones. Aliphenylbenzyloxy-4- (2- (5-phenylpentyloxy)) phenyl] cyclo- hexanone as an oil (5.6 g, 87%) of 2-benzyloxy-4- E5E (5-phenylpentyloxy27] bromobenzene (4.0 g, 9.4 mmol).

IR: (oHCl) 1712, 1616 and 1592 cm -1.

Ms = m / e 432 (M0, 551, 525, 296, 278, 255, 205 and 91).

Trans-5-Albenzyloxy-4- (4,4-dimethylheptyl) -phenylphosphine methylcyclohexane in the form of an oil (5.44 g, 64%) of 2-benzyl- oxy-4- (4,4-dimethylheptyl) bromobenzene (7.85 g, 0.0204 mol) ooh 4-methylcyclohex-2-enone (2.24 g, 0.0204 mol).

IR; (cHo1) 1712, 1615 and 1575 Cm Ms; m / 6,420 (mf), 565, 555, 529, 275, 271 and 91. §F1ÉÄbenzyloxy ~ 4- (4,4-dimethylheptyl) fegygjlcyclopentanone as an oil (5.5 g, 58%) from 2-benzyloxy-4- (4,4-dimethyl- heptyl) bromobenzene (6.0 g, 15.4 mmol), Rf = 0.45 (0.25 mm silica gel, eluting with 4: 4 ether hexane). N-cycloheptanone 4- (4,4-dimethylheptyl) phenyl] Cycloheptanone as an oil (2.94 g, 46%) of 2-benzyloxy-4- (4,4-demethyl- heptyl) bromobenzene (6.00 g, 45.4 mmol) and cycloheptenone (4.69 g, 45.4 mmol). '~ 5- (2,4-Dibenzyloxyphenyl) cyclohexanone in the form of a solid substance (47.9 g, 40%), mp 408-409 ° C; from 4-bromo-2,4 ~ dibenzyloxybenzene (45 g, 0.446 mol) and cyclohexeaâ-enone (44.4 g, 0.446 mol). The product was recrystallized from ether-pentane.

IR; (c fi olš) 1709, 1616 and 1595 cmfl.

NS: m / e 295, 484 and 94.

Analysis -% _C% H calculated for C26H2605 80.80 6.78 found 80.88 6.80 'IO 15 20 25 50 55 40 7899060-2 29 Benzyloxy-4- (1,1-dimethyloctyl) fegyl] cyclohexanone in the form of an oil (5.0 g, 46%) from 2fl-benzyloxy-4-bromophenyl7- -2-methylnonane (fl0.4 g, 0.0258 mol) and 2-cyclohexen-1-one (2.48 g, 0.0258 mol).

IR: (chciš) 4745, 4848 and 457? cm "".

Ms; m / 8 420 (M +), 577, 529 and 524, aphenobenyloxy-4-t-butylphenyl7cyclohexanone in the form of a oil (27.6 g, 58%) from 2- (5-benzyloxy-4-bromophenyl) -2-methyl- propane (45.4 g, 0.142 mol) and 2-cyclohexen-1-one (45.9 g, 0.445 mol). 5 Ih = (c fl ci) 4724, 4825 and 4582 cm ms; 558 (M *), 524, 295, 245 and 94. benzylobenzyloxy-4- (4,4-dimethylpropyl) phenyl] cyclohexanone as an oil (15.8 g, 65%) of 2- (5-benzyloxy-4-bromophenyl) - 2-methylbutane (24.0 g, 0.0724 mol) and 2-cyclohexen-1-one (7.06 5, 0.0755 mol).

IR; (Choi) 4748, 4848 and 4575 cm

Ms: ih / c 550 (mf), 555, 524, 507, 259 and 94. β-benzyloxy-4- (4,1-dimethylbutyl) phenyl] cyclohexanone in the form of an oil (15.4 g, 42%) from 2- (5-benzyloxy-4-bromophenyl) 2-methylpentane (54.8 g, 0.400 mol) and 2-cyclohexen-1-one (40.5 g, 0.110 mol).

IR: (oHCl) 4758, 4854 and 4592 cm -1.

Ms; o / c 584 (M *), 524, 275 and 94.

Trans-5-1-benzyloxy-4- (1,4-dimethylheptyl) phenyl] -4- (2- Cropenyl) cyclohexanone as an oil (58.5 g, 70%) of 4- bromo-2-benzyloxy-4- (4,4-dimethylheptyl) bromobenzene (75.0 g, 0.488 mol) and 4- (2-propenyl) -2-cyclohexen-1-one (25.5 g, 0.788 mOl).

IR; (cHc15) 4742, 4845, 4845 and 4575 cm ms; m / c 448 (M +), 580, 554 and 94. Aphenibenzyloxy-4- (4,1-dimethylpentyl) femyl cyclohexanone in the form of an oil (4¶, 5 g, 57%) from 2- (5-benzyloxy-4-bromophenyl) -2-methylhexane (29.6 g, 0.0848 mol) and 2-cyclohexen-4-one (8.65 g, 0.09 mol).

IR; (CHG15) 4750, 4829 and 4592 cm-1.

Ms; m / c 578 (Mi), 555, 524, 287 and 94. Acylbenzyloxy-4- (1,4-dimethylhexyl) phenyl] Cyclohexanone in the form of an oil (11.0 E, 55%) from 2- (5-benzyloxy-4-bromophenyl) - 2-methylheptane (50.2 g, 0.0806 mol) and 2-cyclohexen-4-one (8.5 g, 0.0886 mol).

OD CD V) 10 45 20 25 50 40 C20-2 EQ 12; (CHC15) 1715, 1625 ooh 1585 om "“.

Ms: m / o 592 (M +), 548, 521, 501, 259 ooh 91. ethylenebenzyloxy-4- (1,1-dimethylnonyl) phenyl] cyclohexanone in the form of an oil (45.5 g, 45%) of 2- (5-benzyloxy-4-bromo- phenyl) -2-methyldecane (50.5 g, 0.075 mol) and 2-cyclohexene-4- on (7.1 g, 0.0805 mol).

IR: (number) 1715, 1625 or 1582.

Ms: m / o 454 (mf), 542, 521 ooh 91. α1eabenzyloxy-4- (4,1-dimethyldecyl) phenylylcyclohexanone in the form of an oil (7.0 2, 4?%) from 2- (5-bonsyloxy-4-bromophony) - 2-methylundecane (40.0 g, 0.0928 mol) and 2-cyclohexen-4-one (9.8 g, 0.102 mol).

IR: (cHc15) 1715, 1625 ooh 1585 omkq.

Ms: m / o 448 (M +), 521 ooh 91. 5β-benzyloxy-4- (4,4-dimethylundeoyl) phenyl7-cyclohexanone in the form of an oil (41.5 g, 40%) of 2- (5-benzyloxy-4-bromophenyl) - 2-Methyldodecane (27.5 g, 0.062 mol) and 2-cyclohexen-1-one (6.68 g, o, o6s2 moi). _ IR; (chciš) 1718, 1625 ooh 1585 om '“.

Ms: m / o 462 (M +), 417, 571, 521 ooh 91. α-β-benzyloxy-4- (1,4-dimethylheptyl) phenyl] cyclooctanone as an oil (10.6 g, 65%) from 2- (5-benzyloxy-4-bromophenyl) - 2-methyloctane (¶5.0 g, 58.6 mmol) and 2-cycloocten-4-one (4.78 g, 58.6 mmol).

IR: MS: (mm%) 1m5,% aamh1æ7mf¶ m / o 454 (Mb, 477, 565, 549, 545. 526 and 91.

Example 2: (N- (1,1-dimethylheptyl) -2-hydroxy-phenyl] cyclohexanone A mixture of 49.5 (0.0468 mol) 5-ŧ; benzyloxy-4- (4.1- dimethylheptyl) phenylycyclohexanone, 12.5 g of sodium bicarbonate, 5.00 g of catalyst (40% palladium-on-carbon) and 250 ml of ethanol was stirred under hydrogen at a pressure of 4 atmospheres for 1.5 hours.

The reaction mixture was then filtered through diatomaceous earth with ethyl acetate and the filtrate was evaporated. The raw, solid in- the evaporation residue was purified by column chromatography of 280 g of silica gel and elution was performed with 20% ether cyclohexane, whereby a solid was obtained. Through recrystallization of this solid from aqueous ethanol gave 9.4 g (62%) of the title compound (with the title compound) the association "is referred to here and hereinafter as the title of 40 15 25 35 40 7809069- 5) 51 the relevant section or example specified association) with a melting point of 87 ° C, mainly in the hemiketal form.

IR; (tub) 5226, 4629 and 4580 6m “1.

(CHCl 3) 5571, 5289, 1704, 1625 and 1575 cm -1.

Ms = m / 6 546 (M +), 298, 275 and 254.

Analysis -% C% H calculated for C 24 H 52 O 2 79.70 10.19 found 79.69 9.89 The procedure described above was repeated but using reversal of the appropriate reaction components listed in Example 1 for the manufacture of the following products: § (1,1-dimethylheptyl) -2-hydroxyphenyl] 5-methylcyclo- hexanone as an oil (54 mg, 86%) from 80 mg (0.19 mmol) 5-Albenzyloxy-4- (1,1-dimethylheptyl) -phenyl] 15-methylcyclohexanone. 1a = (CH015) 5597, 5590, 4625 and 4572 6m "1.

Ms; m / 6 550 (rf), 545, 287 and 245.

Trans-5β1a (1,1-dimethylheptyl) -2-hydroxyphenyl] Ä4-methyl- cyclonexanone (825 mg, 99%) mp 62-64 ° 0 (after tender crisis numbering in pentane) from trans-5- [E-benzyloxy-4- (1,1-dimethyl- heptyl) phenyl7 ¥ 4-methylcyclohexanone (1.05 g, 2.50 mmol).

IR: (CHCl 3) 5571, 5555, 1721 (weak), 1626 and 1577 cm -1.

NS: m / e 550 (M +), 512, 288, 275, 245, 205 and 161.

Analysis - . % C% H calculated for C 22 H 34 O 2 79.97 10.57 found 80.55 10.30 §7ZÃ ¥ 1,1-dimethylheptyl) -2-hydroxyphenyl7cyclopentanone (0.54 g, 47%) mp 64-62 ° 0 (after recrystallization. 1 pentane) from 5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclopentanone (1150 ga 5485 mm01) ~ IR: (Kßr) 5279, 1759, 1621 and 1577 cm -1.

Ms: m / 6 502 (M +), 285, 247, 489, 475 and 464.

Analysis -% C% H calculated for C2 OH5OO2 79.42 10.00 found 79.55 10.05 Ephrathene (1,1-dimethylheptyl) -2-hydroxyphenylycloheptanol (795 mg, 65%), mp 78-79 ° C (after recrystallization) pentane) from 5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl70cyclo- heptanone (1.6O g, 5.80 mmol).

IR; (c fl ciš) 5574, 5289, 4704, 4624, 4605 and 4577 cm "“.

MS: m / 6 550 (M +) and 245. \ 1 co 5 40 45 20 50 55 ,, co hrs. rr IN wa 52 Analysis -% 0% H calculated for C22H54O2 79.95 40 »57 found 79.60 * 40.55 Quantitative yield, if necessary, 5-pharyngeal nyarexi-4- (2- (5-phenyl) Qentïloxy2pheny17b1kl0hexanone in the form of an oil from 5- [eel benzyloxy-4- (2- (5-phenylpentyloxy)) phenyl] cyclohexanone (1.0 g, 2.26 mmol). 1R = (CHCl 3) 5571, 5555, 1709, 1625 and 1587 cm -1. m6 = m / e 552 (M +), 206, 188 and 91. 5- (2,4-dihydroxyphenyl) cyclohexanone in the form of a solid substance (8.5 g, 94%), melting point = 458 ° C (after recrystallization in isopropyl ether) from 5- (2,4-dibenzyloxyphenyl) cyclohexanone (46.9 g, 45.7 mmol).

IR; (rst) 5195, 1651 and 1605 em'4.

Ms: m / e 206 (PF), 188, 165, 149 and 156.

Analysis -% C% H calculated for C 2 Hq 4 O 5 69.88 6.84 found 69.94 6.78 § (4,4-dimethyloctyl) -2-hydroxyphenyl70cyclohexanone (0.75 g, 48%) from 2.00 g (4.76 mmol) of 5-β-benzyloxy-4- (1,1- dimethyloctyl) phenylbyclohexanone. Melting point 78-80 ° C (after omkrist. and pentane). X) IR; (GHC15) 5571, 5555, 1709 (e), 1626 and 1577 cm-4. ns; m / e 550 (rf), 514, 512, 287 and 251; 5Analysis ~% C% H calculated for C 22 H 54 O 2 79.95 40.57 füllnet 5- (4-t-butyl-2-hydroxyphenyl) cyclohexanone (4.22 g, 58%) from 5- (2-Benzyloxy-4-t-butylphenyl) cyclohexanone (40.0 g, 0.0298 “Me1. mp 177-178 ° C (after tmkriet. 1 ether).

IR; (Cat) 5279, 1659 and 1592 em „4.

NS! m / e 246 (M +), 254, 228, 245, 245, 205, 489, 476 a 161._ Β-ethyl (4,4-dimethylpropyl) -2-hydroxyphenylphyclohexanone (2.52 g, 45%) from 5-Ealbenzyloxy-4- (4,1-dimethylpropyl) phenyl] eyklenexenone (7.50 g, 0.0214 flour). melting point 165-166 ° 0 (after crystallization in isopropyl ether).

In; (OH1) 5656, 5401, 1724 (e), 1654 and 1587 cm-4.

NS: m / e 260 (Ni), 242, 254, 247, 245 and 464.

X) (s) 3 weak 10 15 20 25 50 55 40 55 Marys -% c 5 ef »H calculated for C 17 H 24 O, 78.42 9.29 found 73.47 9.32 (1,1-dimethylbutyl) -2-hydroxyphenyl] cyclohexanone (0.6 g, 11%) from 5-β-benzyloxy-4- (1n-dimethylbutynphenyl) cyclohexanone (7.00 g, 0.0192 mol). Melting point 101-102 ° C (after recrystallization from isopropyl ether).

IR: (CHCl 3) 5656, 5401, 1724 (s), 1654 and 1585 cm -1.

Ms; m / e 274 (W), 256, 251 and 215.

Analysis -% C% H calculated for 018112602 78.79 9, 55 found 78.78 9.21 Trans-5- [4- (1,1-Dimethylphenyl) -ethyroxyphenyl] gropylcyclohexanone (1.0 g, 76%) as an oil from the trans- 5-β-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -4- (2-propenyl) cyclop hexanone (1.65 g, 5.69 mmol). m; (011015) 5610, 5590, 1716 (Weak), 1629 and 1577 om ”. ns; m / e 556 (FF), 540, 288, 275, 255, 205 and 161. § (1,1-dimethylpentyl) -2-hydrophenylphenyl7byclohexanone (4.0 g, 95%) of 5-Aenebenzyloxy-4- (1,1-dimethylpentyl) phenyl74 cyclohexanone (5.5 Å, 0.0146 mol). Melting point 124.5-125.5 ° C (after recrystallization in pentane).

IR: (CHCl 3) 5625, 5578, 1718 (Weak), 1654 Odh 1587 cm -1.

Ms; m / e 266 01+), 245 and 251.

Analysis -% C% H calculated for Cq9H28O2 79.42 9.79 5 found 79, 52 9, 55 Phyl (1,1-dimethylhexyl) -2-hydroxyphenyl70cyclohexanone (quantitative yield) from 5-benzyloxy-4- (1,1-dimethylhexyl) - phenylbyclohexanone (2.0 g, 5.1 mmol), mp 82-85 ° C.

IR; (011015) 5656, 1654, 1616 and 1565 if '. us; fi / e 502 01+), 284, 259 and 251.

Analysis -% C% H calculated for C2OH3OO2 79.42 10.00 found 79.15 9.75 5 [(1,1-dimethylnonyl) -2-hydroxyphenyl] cyclohexanone (2.4 g, 61%) from 5-tribenzyloxy-4- (1,1-dimethylphenyl) phenyl] cyclohexanone (5.0 g, 11.5 mmol). Melting point 72-5.5 ° C.

IR; (011015) 5650, 5415, 1721 (weak), 1659 and 1595 cm ”.

HRNEI m / 6 544.2691, (M +, C 25 H 56 O 2), 526.257O 0Ch 501.2168.

OD 10 15 20 25 50 55 40 * Û -2 CD Û \ one 54 57β (1,1-dimethyldecyl) -2-hydroxyphenylyclohexanone (880 mg, 55%) from 5-Albenzyloxy-5- (1,1-dimethyldoyl) phenyl] 1l cyclohexanone (2.0 g, 4.46 mmol). Melting point 78-79 ° C.

IR: (CHCl 3) 5625, 1629, 1616 and 1587 cm -1. mms; m / e 5582856 (MÅ 02485802). 5β (1,1-dimethylundecyl) -2-hydroxyphenylphyclohexanone (1.49 g, 46%) from 5-1-benzyloxy-4- (1,1-dimethylundecyl) phenyl cyclohexanone (4.00 g, 8.66 mmol). Melting point 72-75 ° C. (rar) 5268, 1629 and 1580 6m "“.

IB: Ms: _ @ / 6 572 (M *), 554, 529 and 251.

Analysis - _% C% H calculated for C25H2OO2 80.59 10.82 found 80.70 10.84 57α (1,1-dimethylheptyl) -2-hydroxyphenyl7byclooctanone (1.92 g, 81%) from 5-Lelbenzyloxy-4- (1,1-dimethylheptyl) -phenyl cyclooctanone (5.02 g, 6.95 mmol). Melting point 118 ° C.

IR; (cHc15) 5625, 5558, 1709, 1629 and 1587 6m ''. ms; m / 6 544 (M *), 529, 526, 285, 275, 259 and 241.

Analysis -% C% H calculated for 02585602 80.18 10.55 found 79.92 10.57 5-Phyl (1,1-dimethylheptyl) -2-hydroxyphenyl] -4-methyl-2- cyclohexen-1-one (1.15 g, 70%) of 5-ethylbenzyloxy-4- (1,1-di- methylheptyl) phenyl7,4-methyl-2-cyclohexen-1-one (2.1O g, 5.02 mmol). Melting point 111 ° C (after recrystallization from diisopropyl ether) petroleum ether). 1 IR: (CHCl 3) 5554, 5279, 1667, 1625 and 1567 cm -1.

Ms: m / 6 528 (M +), 515 and 245.

Analysis - 0% 0% H calculated for C 22 H 32 O 2 80.44 9.85 found 50.55 9.67 Example 5: cis-5-Albenzyloxy-4- (1,1-dimethylheptyl) -phenyl] bicyclo- hexanol and the trans isomer thereof. To a solution of 45.0 g r (0.66 mol) 5-Aislobenzyloxy-4- (1,1-dimethylheptyl) phenyl7byclo- hexanone in 500 ml of methanol and 15 ml of tetrahydrofuran, which solution had a temperature of -40 ° C, was added in three portions 8.05 g (0.212 mol) of sodium borohydride. The reaction mixture was stirred for 1 hour at -40 ° C, after which its temperature was allowed to rise to -10 ° C. Thereafter, the reaction was quenched by the addition of 40 45 50 55 7809060-2 55 400 ml of a saturated sodium chloride solution and the reaction mixture The mixture was added to 4500 ml of water and extracted with ether (5 x 450 ml). The combined ether extracts were washed with water (5 x 400 ml) and with a saturated sodium chloride solution (2 x 200 ml). Then, drying was performed with magnesium sulfate and evaporation to give an oil. This was purified by column chromatography on 400 g of silica gel. Elution was carried out with 20% ether-cyclohexane and was obtained as a yield (a) first 5.0 g (42%) of trans-5-α-benzyloxy-4- (4,4-dimethyl- heptyl) -phenylphyclohexanol.

IR; (oHc1) 5656, 5497, 1629 and 1587 cm -1.

MS = m / e 408 (MD, 595, 590525 and 91- Analysis -% C '% H calculated for C 28 H 50 O 2 82.50 9.87 found 84.98 9.82 (b) and then 22.2 g (54%) of cis-5-β-benzyloxy-4- (4.4- dimethylheptyl) phenyl7cyclohexanol; mp 75.5-76.5 ° C.

IR; (cHc1) 5858, 5497, 1629 and 1587 cm -1.

M8; m / c 408 (M +), 595, 590, 525 and 91.

Analysis -% C% H calculated for c28H4Oo2 82.50 9.87 found 81.95 9.74.

The following compounds are prepared in the same manner from those of Example 4 the appropriate ketones.

A quantitative exchange of §¿§; ¿Élbens loxi-4- 4 4-di- methylheptyl) phenyl 17 -5-methylcyclohexanol in the form of an oil 5-Albenzyloxy-4- (4,4-dimethylheptyl) phenylphen-5-methylcyclohexanone (200 mg, 0.476 mmol).

Ia; (cnciš) 5548, 5578, 1805 and 1555 cm

Ms; m / c 422 (M +>, 557, 514, 299, 271 and 229. trans, transf- [Albenzyloxy-4- (4,4-dimethylheptyl) -phenyl] 4-methylclohexanol (0.225 g, 44%) as an oil and 4.49 g, (74%) of the cis trans isomer of trans-5-Albenzyloxy-4- (4,4- dimethylheptyl) phenyl 17,4-methylcyclohexanone (4.6 g, 5.8 mmol). §Ra22, §r2n§ = PNB: egg yolk 0.80 (m, terminal side chain methyl and 0-4- methyl), 4.27 (s, gem-dimethyl), 5.42 (m, benzylic methine), 4.20 (m, carbinolmethine), 5.45 (s, benzyl ether methylene), 6.95 (m, ArH), 7.15 (d, J = 8Hz, ArH) and 7.48 (DS, PhH). 03 'lO 15 20 50 55 40 va in.. '7.45 (bs, Ph fl). q'u-9 gI_ 2 56 IR: (OHCl) 5415, 1616 and 1575 ms: m / e 422 (rf), 407, 557, 514, 272, 229 and 91. g _: _ 'L_§, trans: P88; 8g% §1 0.70 (8, J = 6Hz, 0-4 mefiyl), 0.85 (m, ter- minial zaokeajemšcyl), 1.29 (S, gem-aimecyl), 2.81 (m, ben- cyclic methine), 5.75 (m, carbinolmethine), 5.15 (s, benzyl ether methylene), 6.95 (m, ArI-I), 7.15 (d, J = 8Hz, ArH) and 7.45 (bs, Eh fl). 618; (GHC15) 5571, 5590, 1618 and 1577 cm Ms: m / e 422, 557, 514, 272, 229 and 91.

A mixture of gig and trans 5y1ÉÄbensvl0xy-4- (1,1 ~ dimethylheptyl) fgyi fl mfclopentanol (1.1 g, 85 91 :) in the form of a oil from 5-β2Benzyloxy-4- (1,1-methylheptyl) phenyl; tanone (1.52 g, 5.57 mmol).

Ms: m / e 594 (M +), 579, 576, 509 and 91.

'IN c Trans-5-12-90 en syloxy-4- (1,1-dimethylheptyl) ethylene cyclo- heptanol (695 mg, 49%) and 580 mg (27%) of the cis isomer in form of oils from 5- [2-benzyloxy-4- (1-dimethylheptyl) -phenyl} -7- cycloheptanone (1.40 g, 5.55 mmol). §Lâ = _ PMR: loop 0.85 (m, terminal side chain methyl), l1.50 (s, gem-dimethyl), 5.15 (m, benzylic methine), 5.90 (m, carbinol- methine), 5.615 (s, benzyl ether methylene), 6.8-7.4 (m, ArH) and IR; (0Hc15) 5571, 5448, 1615 and 1572 cmfq.

Ms; m / e 422 (M +), 557, 514, 229 and 91. ÉEšE§ = PN; eyeball 0.86 (m, terminal methyl), 1.26 (S, gem-di- methyl), 5.41 (m, benzylic methine), 4.10 (m, carbinolmethine), 5.17 (s, benzylic methylene), 6.8-7.2 (m, ArH), 7.18 (d, J = 8Hz, ArH), and 7.45 (bs, PhH).

IR: (Cyclic) 5554, 5590, 4615 and 1572 cm-1 ms = m / e 422 (m *), 557, 551, 514, 246, 229 and 91. cis-5-jf-benzyloxy-4- (2-5-phenylpentyloxy) family-cyclo- hexanol (1.51 g, 76%) and the trans isomer (0.579 g, 19%) in form of Oils of 5-1,2-benzyloxy-4- (2- (5-phenylpentyloxy)) - phenyl] -17- cyclohexanone (2.0, 4.52 mmol).

E222§ = 1 PNB; öäšâl 1.28 (8, J = 6Hz, methyl), 2.68 (m, benzylic methylene), 5.45 (m, benzylic methine), 4.22 (m, carbinolmethine), 10 15 50 55 40 7809060-2 57 4.50 (m, side chain methine), 5.09 (s, benzyl ether methylene), 6.45 (dd, J = 8 and 2 Hz, ArH), 6.55 (bs, AlH), 7.10 (d, J = 8Hz, AlH), 7.25 (s, PhH) and 7.45 (bs, PhH).

IR: (CHCl 3) 5571, 5448, 1615 and 1590 cm -1.

Ms; m / S 444 (f), 298, 280, 190 and 91. cls: PNB: aäšâl 1.25 (d, J = eHz, methyl), 5.0 (m, bSnSy1iSk methine), 5.77 (m, carbinolmethine), 4.58 (m, side chain methine), 5.10 (S, bShSy1etSrmetin), 8.50 (da, J = 8 and 2Hz, Arn), 8.58 (bsa ArHJa 71.12 (d, J = 8HZ1 -Arïni 7952 (sa PhH) Och 7945 (Sa PhH).

IR: (CHCl 5) 5571, 5590, 1615 and 1587 cm -1.

Ms; m / S 444 (M +), 298, 190 and 91. cis-5-benzyloxy-4- (1,1-dimethyloctyl) phenyl] cyclo hexanol (1.55 Å, 45%) and the trans isomer (0.5 g, 11%) 5.00 g (7.14 mmol) 5-β-benzyloxy-4- (1 (% dimethyloctyl) phenyl] cyclohexanone and 0.90 g (50%) of a cis-trans mixture. ÉEëEâ = PM: aggsl 0.87 (m, terminal Sidokeajemethyl), 1.25 (S, gem-dimethyl), 5.50 (m, benzylic methine), 4.22 (m, carbinol ~ methine), 5.15 (s, benzyl ether methylene) and 6.8-7.6 (m, ArH odh PhH).

IR; (CHCl 3) 5497, 1825 and 1582 Sm'1.

Ms; m / 8 422 (M5) and 525. cis: PM: ace 0.85 (m, Sidokeajemethyl terminal), 1.25 (S, gem-dimethyl), 5.0 (m, benzylic methine), 5.75 (m, carbinol- methine), 5.12 (s, benzyl ether methylene), 6.91 (dd, J = 8 and 2Hz, ArH), 6.91 (d, J = 2Hz, AlH), 7.17 (d, J = 8Hz, -ArH) and 7.42 (bs, PhH).

IR; (cncl) 5571, 5425, 1818 and 1577 Sm „1. ms; m / S 422 (M +) and 525. Ois-5- (2-benzyloxy-4-t-butylphenyl) glycolhexanol (?, 18 g, 59%) and the trans isomer (1.55 g, 11%), and 1.5 g (12%) of a mixture of the cis and trans polymers from 12.0 g (0.0557) mol) 5- (2-benzyloxy-4-§; butylphenyl) cyclohexanone. gig: Melting point: 78-79 ° C (after recrystallization from hexane) PM0 = aggâl 1.50 (S, gfbutyl), 5.10 (m, benSy1iSk mevin), 5.72 (m, carbinosmethine), 5.12 (s, benzyl ether methylene), 6.97 (d, 9 7SC9060-2. 'lO 45 20 25 50 58 J = 2Hz, Ar fl), 6.97 (ad, J = 6 and 2Hz, Arn), 7.17 (6, J = 6Hz, ArH) and 7.40 (bs, PhH). ' IR; (GHC15) 5656, 5472, 1621 and 1562 6m "".

Ms: m / 6 556 (M +), 525, 520, 250, 215 and 91. mmws -% C% H calculated for C 25 H 30 O 2 81.64 8.95 found 61.79 6.77 Éšëåâï Phu: Agsal 1.25 (S, gfhuhyl), 5.50 (m, benzylic) methine), 4.20 (m, carbinolmethine), 5.02 (s, benzyl ether methylene) and 6.8 - ?, ¿| - (m, ArH and PhI-I).

IR; (CHG15 5650, 5472, 1626 and 1567 cmfq.

Ms: m / 6 556 (M +, 525, 520, 250 and 91). Cisβ5β-benzyloxy-4- (1,1-dimethylpropyl) phenyl] -cyclo- hexanol (6.5 g, 78%) and the trans isomer (1.0 g, 12%) in form of oils from 8.0 g (0.0229 mol) of 5-Albenzyloxy-4- (1,1-dimethyl) propyl) phen3¶]% ykl0hexan0n. 1 Eiâ * ' 9 PNB: öâšâlš 0.67 (6, J = 7Hz, terminal methyl), 1.26 (s, ' gem-dimethyl), 5.05 (m, benzylic methine), 5.75 (m, carbinol methine), 5.45 (s, benzyl ether methylene), 6.92 (d, J = 2, ArH), 6.92 (ad, J = 6 and 2Hz, Ar fl), 7.17 (6, J = 6Hz, Arn) and 7.42 (hs, PhH). 1R = (cnclš) 5656, 5544, 1626 and 1567 cm "". ns; m / 6 552 (M *), 557, 554, 525, 244, 215 and 91. Éåêšâ * IR; (CHCl 3 5656, 1626 and 1567 6m Ms = m / e 552 (M0, 557, 554, 525, 244, 215 and 91. cisf5-β-benzyloxy-4- (1,1-dimethylbutyl) phenyl] cyclohexanol (4.46 g, 52%) and the trans isomer (0.88 g, 11%) and 0.49 g (6.4%) of a mixture of the cis and trans isomers in the form of oils from 8.0 g (0.022 mol) of 5-Albenzyloxy-4- (4,1-dimethyl- butyl) pheny17oykl0hexan0n.

Såå *.

PNB; 6§% §l_ 0,60 (m, terminal methyl), 1,25 (S, gem-die methyl), 5.05 (m, benzylic methine), 5.70 (m, carbinolmethine), 5.08 (s, benzyl ether methylene), 6.86 (d, J = 2Hz, ArH), 6.86 (dd, J = 6 and 2Hz, Arn), 7.11 (6, J = 6Hz, ArH) and 7.55 (bs, Ph fi). 1R = (cHc15) 5625, 5446, 1621 and 1562 cmfq.

M6; m / 6 566 (M *), 551, 546, 525, 256, 215 and 91. 59 7809060-2 trans! PMn = δ 0.65 (m, terminal mooyl), 1.22 (6, gum-oi- methyl), 5.40 (m, benzylic methine), 4.18 (m, carbinolmethine), 5.09 (s, benzyl ether methylene), 6.86 (d, J = 2Hz, ArH), 6.86 (dd, Δ = 6 ooh 2Ho, Arn), 7.11 (o, J = 6Hz, ArH) ooh 7.59 (m, PhM).

IR: (CHCl 5) 5625, 5472, 1625 and 1585 cm -1.

Ms; o / o 566 (MÜ, 551, 546, -525, 256, 215 ooh 91. trans-5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl] -is- 4- (2-propenyl) cyclohexanol (1.9 g, 15%) and cis-5, trans-4- Isomer (7.5 g, 51%) in the form of oils from trans-5-β-benzyl- oxy-4- (1,1-dimethylheptyl) phenyl] -4- (2-propenyl) cyclohexanone (14.5 g, 52.1 mmol). When eluting from silica gel with the following: ether 2: 1 was first obtained the trans-5, cis-4 isomer of the title compound the unit in the form of an oil and then the cis-5, trans-4-isomer. Trans-5, cis-4 isomers: IR; (CMC15) 5559, 5401, 1659, 1606 ooh 1567 om '“.

Ms: h / o 446 (M +), 455, 450, 565, 406 ooh 91.

PMM = total 0.62 (m, terminal motile), 1.25 (6, gum-oi- methyl), 5.50 (m, benzylic methine), 4.12 (m, carbinolmethine), Û0 4.6 ~ 5.0 (m, vinyl H), 5.06 (s, benzylic methylene), 5.2-6.1 (m, vinyl-H), 6.82 (d, J = 2Hz, ArH), 6.82 (dd, J = 8 and 2Hz, AIH), 7.07 (d, _J = 8Hz, AIH) and 7.58 (bs, Ph). _ cis-5, trans-4-isomerase _ IR: (chclg) 5571, 5401, 1659, 1610 ooh 1572 om ”.

Ms; m / o 446 (MW, 406, 565 ooh 91).

PNB: weight 0.82 (m, terminal methyl), 1.22 (s, gem-di ~ methyl), 2.90 (m, benzylic methine), 5.75 (m, carbinolmethine), 4.6-5.1 (m, vinyl-H), 5.02 (s, benzylic methylene), 5.5-6.5 (M, vinyl-H), 6.75 (d, J = 2Hz, Ar fi), 6.75 (da, J = 6 ooh 2Hz, 50 ArH), 6.99 (a, J = 6Hz, ArH) or 7.25 (bo, Ph). cis-5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl] trans- 4- (2-botony1) oyl <1ohoxoho1 (495 mg, 62%) ooh isomers (105 mg, 18%) of trans-5-Albenzyloxy-4- (1,1-di methylheptyl) phenylyl (2-butenyl) -cyclohexanone (600 mg, 1.50 55 mmol). The trans-5, cis-4 isomer was eluted first. trans-5, cis-4 isomers = Ms; m / o 462 (MÜ, 447, 444, 577 ooh 91. cis-5, trans-4-isomers: - m; (chclš) 5610, 5446, 1616 ooh 1577 oufq. 40 Ms: m / o 462 (M +), 447, 444, 577 ooh 91. | \.) 31 »<1 oo <3 * Q 10 ' 45 20 50 55 40 m. ._ - . »\ F) IN EQ 40 cis-5-Albenzyloxy-4- (1,4-dimethylheptyl) phenyl 4- (2-pentenyl) cyclohexanol and the trans-5, cis-4-isomer from trans-5- (2-benzyloxy-4- (1,1-dimethylheptyl) phenyl) -4- (2-pentenyl) ~ cyclohexanone (497 mg, 1.04 mmol). Upon elution was first obtained 84 mg (47%) of the trans-5, cis-4-isomer (Rf = 0.26, silica) gel, 55% ether-pentane) and 565 mg (75%) of cis-5, trans-4-iso- mers (Rf = 0.45, silica gel, 55% ether-pentane). cis-5-Albenzyloxy-4- (1,4-dimethylpentyl) phenyl] cyclo- hexanol (5.0 g, 85%) and the trans isomer (0.6O g, 40%) in form of oils from 5-β-benzyloxy-4- (1,4-dimethylpentyl) phenylcyclo- hexanone (6.0 g, 58 mmol).

Ešåšâ * IR: (CHCl 3) 5656, 5497, 1625 and 1582 cm -1.

Ms; m / e 580 (M +). ' Pma = öägâl 0.85 (m, terminal meryl), 1.24 (S, gem- dimethyl), 5.5 (m, benzylic methine), 4.20 (m, carbinolmethine), 5.09 (s, benzylic methylene) and 6.8-7.6 (m, ArH). cis: 1 IR: (CHCl 3) 5636, 7621 ° C 4580 cm -1.

Ms; m / 6,580 (NF).

PNB: δ 0.75 (m, terminal methyl), 1.14 (s, average dimethyl), 2.90 (m, benzylic methine), 5.52 (m, carbinolmethine), 4.8o (S, benzylic acid), 6.49 (da, J = 8 and 2Hz, Ar fi), 6.49- (d, J = 2Hz, Ar fi), 6.72 (a, J = 8Hz, Arn) and 6.96 (bs, Ph). cis-5-β> benzyloxy-4- (1,1-dimethylhexyl) phenylcyclo- hexanol (5.0 g, 45%) and the trans isomer (660 mg, 9%) in form of oils from 5-α-benzyloxy-4- (1,4-dimethylhexyl) -phenyl] cyclo- hexanone (7.0 g, 17.9 mmol). cis: IR: (cnclš) 5625, 5448, 1618 and 1575 6mT '.

Ms: m / ç 594 (MH +) rm; ÖTHS 0.82 (m, terminal methyl), 1.22 (S, average CDCI cdimethyl), 5.07 (m, benzylic methine), 5.70 (m, carbinolmethine), 5.08 (s, benzylic methylene), 6.88 (dd, J = 8 and 2Hz, ArH), 6.88 (8, J = 2Hz, Arn), 7.12 (a, J = 8Hz, Arn) and 7.57 (bs, Ph). Ššëâ * IR; (GHC15) 5625, 7448, 1618 and 157? cm '“.

M6; m / 6 594 (M +).

PMBI Öggâl 0.80 (m, terminal methyl), 1.27 (s, average dimethyl), 5.42 (m, benzylic methine), 4.12 (m, carbinolmethine), 'IO FO V1 50 55 40 78Û9Û6Û-2 41 5.02 (s, benzylic methylene), 6.85 (m, ArH), 7.04 (d, J = 8Hz, ArH) and 7.54 (bs, ArH). cis-5-α, β-benzyloxy-4- (1,1-dimethylnonyl) phenylygyclo- hexanol (5.0 U, 59%) and the trans isomer (1.0 g, 12%) in form of oils from 5-12-benzyloxy-4- (1,1-dimethylnonyl) -phenyl70yk10- hexanone (8.5 g, 19.6 mmol). åiâ * ' 1R = _ (cHo1¿) 5825, 5448, 1818 and 1577 cm

MS: m / e 456 PMR: δ 0.85 (m, terminal methyl), 1.22 (s, average dimethyl), 5.04 (m, benzylic methine), 5.67 (m, carbinolmethine), 5.08 (s, benzylic methylene), 6.87 (dd, J = 8 and 2Hz, ArH), 6.87 (d, J = 2Hz, ArH) and 7.05-7.45 (m, ArH and Ph). Éåšëâ * IR: (cycles) 5810, 5448, 1818 and 1575 m -1. ms: m / e 458 (M +).

PNB: weight 0.82 (m, terminal methyl), 1.22 (s, average dimethyl), 5.42 (m, benzylic methine), 4.16 (m, carbinolmethine), 5.02 (s, benzylic methylene) and 6.7-7.5 (m, ArH and Ph). cis-5-12-benzyloxy-4- (1,1-dimethylundecyl) phenyl7-cyclo- hexanol (5.5 g, 50%) and the trans isomer (1.0 g, 14%) in form of oils from 5-12-benzyloxy-4- (1,1-dimethylundecyl) phenyl] cyclo- , hexanone (7.0 g, 15.0 mmol). clsz IR = (OHH15) 5858, 5448, 1821 and 1582 m @ 8.

NS: m / e 464 (M &lt; + &gt;).

TMS. _.

PNB: δCDCl 0.95 (m, terminal methyl), 1.55 (s, average dimethyl), 5.09 (m, benzylic methine), 5.70 (m, carbinolmethine), 5.20 (s, benzylic methylene), 6.99 (dd, J = 8 and 2Hz, ArH), 8.99 (aa, J = 8 and 2Hz, Arn), 7.22 (8, J = 8Hz, Arn) and 7.50 ('05, PhH). Éïâëäï IR: (CHCl 3) 5554 (broad), 1818 and 157? cm '“.

MS: m / e 464 (M &lt; + &gt;).

PNB: weight 0.85 (m, terminal methyl), 1.22 (s, average dimethyl), 5.48 (m, benzylic methine), 4.17 (m, benzylic methine), 5.08 (s, benzylic methylene) and 6.75-7.55 (m, ArH and Ph). cis-5-12-benzyloxy-4- (1,1-dimethyldecyl) phenyl7-cyclo- hexanol (2.66 g 59%) and the trans isomer (0.56 g, 8%) in form of oils from 5- [E-benzyloxy-4- (1,1-dimethyldecyl) phenyl] cyclo- hexanone (4.5 g, 10.0 mmol). 10 20 25 50 55 40 3Û "2 42 § 0 IR: (OHc15) 5704, 5571, 1659 and 1597 cm -1.

M8: _m / e 450 (M *).

P88: δ δ 0.86 (m, terminal methyl), 1.25 (S, average dimethyl), 5.08 (m, benzylic methine), 5.74 (m, carbinolmethine), 5.08 (s, benzylic methylene), 6.88 (dd, J = 8 and 2Hz, ArH), 6.88 (8, J = 2Hz, Arn), 7.12 (8, J = 8Hz, Arn) and 7.57 (be, Ph). 22222 * 4 5 IR =, (OHc15) 5625, 5448, 1616 and 1577 cm -1.

Ms = m / 6 450 (M +).

PMR: eye gel 0.82 (m, terminal methyl), 1.22 (8, average dimethyl), 5.55 (m, benzylic methine), 4.22 (m, carbinolmethine), 5.02 (s, benzylic methylene) and 6.8-7.6 (m, ArH and Ph). cis-5-β-benzyloxy-4- (1,1-dimethylheptyl) phenylylocyclo- octanol (15.6 g, 19%) and the trans isomer (4.12 g, 59%) i form of oils from 5-β-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclooctanone (7.0 g, 16.1 mmol).

E: (CHCl 3). - ms: m / e 456 (M *), 421, 418, 551, 528, 500, 245 øch PNB: weight 0.85 (m, terminal methyl), 1.28 (s, average dimethyl), 5.19 (bm, benzylic methine), 5.89 (bm, carbinol- methine), 5.10 (s, benzylic methylene), 6.85 (m, ArH), 7.08 (d, J = 8Hz, ArH) and 7.58 (m, Ph). 91.

E2ë2§ = IR; (cHc1) Ms; m / 6,456 (M +), 421, 418, 551, 528, 245 and 91.

PNB: ÖTMS 0.85 (m, terminal methyl), 1.28 (s, average CDCl dimethyl), 5.4 (bm, benzylic methine), 5.9 (m, carbinolmethine), 5.10 (s, benzylic methylene), 6.85 (m, ArH), 7.08 (d, J = 8Hz, ArH) and 7.56 (m, Ph).

Example 4: 81615-β4L (1,1-methylheptyl) -2-nyarexifegy; 7byk10hexanO1 A mixture of 22.0 g (0.0559 mol) of is-5-β-benzyloxy- 4- (1,1-dimethylheptyl) phenyl] cyclohexanol, 12.0 g of sodium bicarbonate bonate and 2.0 g of 10% palladium-on-carbon were stirred under hydrogen with a pressure.of 1 atmosphere for 2 hours. The reaction mixture is filtered. was filtered through diatomaceous earth with ethyl acetate and the filtrate evaporated to dryness. The solid evaporation solution thus obtained The residue was recrystallized from hexane to give 15.2 g (77%). of the title compound, m.p. 109-110 ° C. \, '1 40 55 40 43 IR, (oncl> 561o, 5556, 1626 and 1562 6n "".

Ms = n / e 516 (MÜ, 5oo, 255 and 215.

Analysis ~% C% H calculated for 02515402 79.19 10.76 found 78, 96 1o, 59 In the manner indicated above, the ones listed below were prepared the compounds from suitable reactants according to examples 5- A ' trans-5-(yl (4,4-dimethylheptyl) -2-hydroxyphenyl] cyclo- hexanol (2.47 g, 74%), mp 424-425 ° C (after crystallization). in pentane) from trans-5-β-benzyloxy-4- (4,4-dimethylheptyl) -phenyl] -phenyl cyclohexanol (4.50 g, 0.044 mol).

IR; (cnclš) 5610, 559o, 1626 och 1575 enfl.

Ms: n / e 516 (W), 50, 255 and 215.

Analysis -% C% H calculated for C 21 H 54 O 2 79.49 40.76 found 78.82 40.45 A quantitative yield of z_-5-¿E-§1,1-dimethyl1hegt112- 2-hydroxyphenyl7,5-methylcyclohexanol, m.p. 90-94 ° C (after omkrist. in petroleum ether) from Z-5-Albenzyloxy-4- (4,4-dimethyl- heptyl) phenyl7 ¥ 5-methylcyclohexanol (480 mg, 0.246 mmol).

IR: (CHCl 3) 5597, 5555, 4605 and 1570 cm -1.

Ms; n / e 552 (W), 514, 299, 286, 271, 247 and 229.

Analysis -% C% H calculated for C 21 H 56 O 2 79.45 40.92 found 79.24 40.64 A quantitative yield of trans, trans-5-β4l (4,4-di- methylheptyl) -2-hydroxyphenyl 17,4-methylcyclohexanol, m.p. 454-455 ° C (after recrystallization from pentane) from trans, trans-5 ~ [ÉÄ benzyloxy-4- (4,4-dimethylheptyl) phenyl714-methylcyclohexanol (490 mg, 0.450 mmol).

IR: (cnclš) 5571, 5555, 1626 and 1575 and ”.

Ms; m / e 552 (IF), 517, 514, 247, 255 6611 229.

Analysis -% C% H calculated for C 22 H 56 O 2 79.46 40.92 found 79.45 40.68 A quantitative yield of cis, trans-5-14 ¥ (4,4-di- methylheptyl) -2-hydroxyphenyl7,4-methylcyclohexanol, m.p. 450 ~ 454 ° C (after recrystallization from pentane) from cis, trans oxy-4- (4,4-dimethylheptyl) phenyl] -4-methylcyclohexanol (4.45 g, 2.72 mmol). 10 15 20 25 50 44 IR: (CHCl 3) 5571, 5555, 1621, 1605 and 1580 cm -1.

M6; m / e 552 (M +), 514, 272, 247. 255 and 229.

Analysis -% 0% H. calculated for C22 H5602 79.46 10.92 found 79.15 10.72 cis-5-yl (1,1-dimethylheptyl) -2-hydroxyphenyl] Cyclo- pentanol (464 mg, 55%) and 228 mg (27%) of the trans isomer in the form of oils from a mixture of cis- and transëš-ÅÉÄ Benzyloxy-4- (1,1-dimethylheptyl) phenylphyclopentanol (1.1 g, 2.79 mmol). gig: PNB: eyelet 0.85 (m, terminal side chain methyl), 1.24 (s, gem-dimethyl)? 5.2 (m, benzylic methine), 4.52 (m, carbinol methine), 6.75 (dd, J = 8 and 2Hz, ArH), 6.81 (bs, overlaps 66.75, Ar fi) and 6.97 (6.J = aHz, Arn).

IR = (OH13) 5571, 5500, 1625 and 1567 cm

M6: m / e 504 Éäšëâ * PNB; sooo, 0.65 (m, terminal side chain methyl), 1.27 (s, gem-dimethyl), 5.60 (m, benzylic methine), 4.55 (m, carbino) methine), 6.78 (bs, overlaps 66.88, ArH), 6.88 (dd, J = 8 and 2Hz, Arn) and 7.10 (0.1 J = 6Hz, Arn).

IR: (CHCl 3) 5571, 5555, 1621 and 1575 cm -1.

M6: m / 6 504 (M +), 266, 219 and 201.

A quantitative yield of trans-5-β4L (1,1-methylethyl- heptyl) -2-hydroxyphenyl; 7cycloheptanol, m.p. 55-57 ° C % trans-5-β-benzyloxy-4- (1,1-dimethylheptyl) phenyl] cycloheptanol (695 masl, 1.64 mmol).

IR; (CHCl 3) 5555, 1621 and 1570 cm -1.

Ms: m / e 552 (rf), 514, 247 0611 229.

Analysis -% C calculated for C 22 H 56 O 2 79.46 10.92 found 79.68 10.62 A quantitative yield of cis-5-β (1,1-dimethylheophyl) - 2-hydroxyphenyl7cycloheptanol, m.p. 105-104 ° C (after conversion christ. i pentane) from cis ~ 5 ~ phenyl; 7byk10heptano1 (580 mg, 0.900 mmol).

IR: (CHCl 3) 5571, 5511, 1621, 1605 and 1580 cm -1. ms; m / 6 552 (mf), 514, 247 and 229.

% HRS 10 15 20 F.) N \ r | 50 55 7809060-2 45 Analysis -% C% H calculated for C 22 H 55 O 2 79.46 10.92 found 79.59 10.72 A quantitative yield of cis; §rÅÉïhydroxy-4- (2- (5: phenylpentyloxy)) phenyl7byclohexanol, m.p. 80-84 ° C (after recrystallization from pentane) from cis-5-β-benzyloxy-4- (2- (5- phenylpentyloxy) phenylbyclohexanol (1.45 g, 5.27 mmol).

IR; (CHCl 3) 5597 5555, 4625 and 4597 cm -1.

Ms: m / 6 554 (M *), 556, 206, 49o and 94.

Analysis -% C% H calculated for CEEHEOO5 77.95 8.95 found 77.95 8.51 Trans-5-N-hydroxy-4- (2- (5-phenylpentyloxy)) - phenylphenyl cyclonexanol (244 mg, 90%), mp 65-70 ° C (after conversion krist. in pentane) from trans-β- [Ebenzyloxy-4- (2- (5-phenyl- pentyloxy)) phenyl7byclohexano1 (0.55 g, 0.754 mmol).

IR; (CHG15) 5597, 5576, 4629 and 4567 @m "".

Ms = m / 6 554 (M *), 556, 206, 490 and 94.

Analysis -% C% H calculated for C25H5OO5 77.95 8.55 found 77.55 8.40 cis-5-(yl (1,1-dimethyloctyl) -2-hydroxyphenyl; 7] cyclo4 hexanol (0.725 g, 68%) from 1.56 g (5.22 mmol) of cis-5- [E benzyloxy-4- (1,1-dimethyloctyl) phenyl] bicyclohexanol. Melting point 100 ~ 101 ° C (after recrystallization from hexane).

IR: (CHCl 3) 5574, 5555, 4626 and 4562 cm -1.

Ms: m / 6 552 (M +), 544, 255 and 245.

Analysis -% C% H calculated for CEEHÖGO2 79.46 10.92 found 79.85 11.05 trans-5-14A (1,1-dimethyloctyl) -2-hydroxyphenyl] cyclo- hexanol (0.55 g, 100%) as a 246 mg oil (0.582) mmol) trans-5-1H-benzyloxy-4- (1,1-dimethyloctyl) phenyl] cyclo- hexanol. Melting point 94-95 ° C (after recrystallization from petroleum ether).

IR; (CHC15) 5650, 5456, 4659 and 4562 cm ““.

Ms; m / e 552 (M +), 544, 255 and 245.

Analysis ~% c% H calculated for 022H56o2 79.46 40.92 found 79.54 10.55 40 45 20 25 55 46 cis-5- (4-t-butyl-2-hydroxyphenyl) cyclohexanol (5.99 g, 7? %) from cis-5- (2-benzyloxy-4-t-butylphenyl) -cyclohexanol (7.4 g, 0.024 mol). Melting point 477-fi78 ° C (after Crisis fi, i isopropyl ether).

IR; (KBr) 5484, 5268, 1654 and 1592 6m '“.

Ms; m / 6 248 (M *), 255, 250, 215, 187, 176, 175 and 161.

Analysis -% C% H ' calculated for c46H2502 77.57 9.74 found '77.00 9.54 h trans-5- (t-butyl-2-hydroxyphenyl) cyclohexanol (0.725 g, 99%) from trans-5- (2-benzyloxy-4-t-butylphenyl) cyclohexanol (4.25 E, 2.96 mm0l) - SmälÜPünkÜ 455 ~ 157 ° C ~ (0mcrist. In isopropyl ether) IR: (CHCl 3) 5625, 5401, 1626 and 1575 cm -1.

Ms; m / 6 248 (M +), 255, 250, 215, 187 and 175.

Analysis% C 7% H calculated for Cq6H24O2 77.57 9.74 found 77.54 9.49 cisf§¿¿Ã1 (fl, 1-dimethylpropyl) -2-hydroxyphegyl gggëggg (1.45 g, 52%) from cis-5-α-benzyl16xi-4- (1,1-dimethyl- propyl) phenylybyclohexanol (6.4 g, 0.0175 mol). Melting point 466-467 ° C (after recrystallization from isopropyl ether).

: R = (xsr) 5509, 5279, 1629 and 1592 6m ““.

M8: m / 6 262 (PF), 247, 244, 255 and 215. 5 trans-5-α (1,1-dimethylpropyl) -2-hydroxyphegyl] cyclo- hexanol (0.50 g, 68%) from trans; -5-β-Benzyloxy-4- (1,1-dimethyl- propyl) phenylybyclohexanol (1.00 g, 2.84 mmol). Melting point 124-425 ° C (after crystallization in isopropyl ether).

IR: (OHH15) 5656, 5415, 1659 and 1585 m @ 6.

Ms; m / 6 262 (M +), 247, 244, 255 and 215.

Analysis -% C%, H calculated for 04782602 77.822 9.99 found 77.54 9.87 cis-5-1α (4,4-dimethylbutyl) -2-hydroxyphegyl] cyclo- Weight (1.9 g, 74%) of cis-5-β-benzyl16xi-4- (1,1-dimethyl) butyl) phenyl; 70cyclohexanol (5.59 g, 9.26 mmol). Melting point 158 ~ 159 ° C (after crisis. 1 penran).

IR, (Kßr> 5509, 5279, 1629 and 1592 6m ''.

Ms: m / 6 276 (M +), 261, 258, 255 and 215. 10 15 50 ~ æ \; "| 40 78090 C \ U-9 47 trans-β-β (4,1-dimethylbutyl) -2-hydroxyphenyl] cyclo- hexanol (0.45 g, 87%) as an oil from trans-3-E1l benzyloxy-4- (4,4-dimethylbutyl) phenyl; 7-cyclohexanol (0.700 g, 4.91 mmol).

IR; (cH015) 5656, 5590, 4629 and 4575 6m "1.

Ms; m / 6 276 (M +), 264, 258, 255 and 245. trans-5-1α (4,4-dimethylheptyl) -2-hydroxyphenyl 4-Cruzylclohexanol (626 mg, 78%) from trans-5-β, benzyloxy- 4- (1,1-dimethylheptyl) phenyl] cis-4- (2-propenyl) cyclohexanol (4.0 g, 2.25 mmol). Melting point 92-94 ° C.

IR: (cH015> 5625, 5590, 4629 and 4576 cm -1.

Analysis -% C% H calculated for cgq fi qoog 79.94 44.48 found 20.40 40.69 cis-5-α (1,1-dimethylheptyl) -2-hydroxyphenyl] trans-4- grogylcyclohexanol (550 mg, 74%) from cis-β-benzyl10xy-4- (4,4-dimethylheptyl) phenyl] trans-4- (2-propenyl) cyclohexanol (950 mg, 2.0 mmol). Melting point 126 ° C (after recrystallization in pentane).

IR: (OH15) 5597, 5590, 4629 and 4575 cm -1.

Ms; m / 6 560 (M +), 545, 542, 275 and 257.

Analysis -% C% H calculated for C 24 H 41 O 2 79.94 11.18 found 79.85 10.95 trans-4-butyl-cis-5-δ (1,1-dimethylheptyl) -2-hydroxy- Cyclylbyclohexanol (522 mg, 80%) from cis-5-β-benzyloxy-4- (4,4-dimethylheptyl) phenyl] trans-4- (2-butenyl) cyclohexanol (500 mg, 1.08 mmol). Melting point 151 ° C (after recrystallization in pentane).

IR; (cHc1) 5656, 5556, 4629 and 4567 cm

Ms; m / e 574 (NU, 556, 502, 269, 272, 274, 257, 247, 255, 217, 187 And 161. trans-4-pentyl-cis-5-111 (1,4-dimethylheptyl) -2-gydroxy- Igygygbyclohexanol (225 mg, 76%) from cis-5-β-benzyloxy-4- (4,4-dimethylheptyl) phenyl] Ethrans-4- (2-pentenyl) cyclohexanol (565 ms, 0.762 mmol). mp 455-456 ° C. cis-5-yl (1,4-dimethylpentyl) -2-hydroxyphenyl] cyclo- hexanol (2.5 g, 60%) from cis-5-β-benzyloxy-4- (1,1-dimethyl- pentyl) phenylbyclohexanol (5.5 g, 0.0144 mol). Melting point 442 DEG-443 DEG C. (after conversion to pentane, isopropyl ether). 40 45 F.) \. '1 50 48 1R = M6: n / e 290 (M *), 272, 255 and 215.

Analysis -% C% H calculated for 049H5002 78.57 10.41 found 78.76 10.11 transf6 (4,4-dimethylpentyl) -2-hydroxyphenyl] cyclo- hexanol (585 mg, 78%) from trans-5-α-benzyloxy-4- (4,4-dimethyl- pentyl) phenyl; 70cyclohexanol (640 mg, 4.68 mmol). Melting point 444 ~ 445 ° C (after recrystallization from pentane).

IR; (GHC15) 5656, 5590, 1651 and 1577 cnfq.

Ms: n / e 290 (M *), 272, 255 and 215.

Analysis -% C% H calculated for Cq9H5OO2 78.57 40.44 found 78.58 10.10 cis-5-(yl (4,4-dimethylhexyl) -2-hydroxyphenyl701-chlorohexanol (2.5 g, 99%) of cis-5-Albenzyloxy-4- (4,4-dimethylhexyl) phenyl cyclonexnol (5.00 g, 7.61 nnol). snälnpnnkt 98-100 ° c (after omkrist. and pentane).

IR; (CHCl 3) 5656, 5567, 1626 and 1587 cm -1.

Ms: n / e 504 (rf), 286, 255 and 215.

Analysis -% C% H calculated for C20H5202 78.89 40.59 found 78.57 10.46 trans-5-β (4,4-dimethylhexyl) -2-hydroxyphenyl] cyclo- hexanol (440 mg, 86%) from trans-5-1β-benzyloxy-4- (4,4-dimethyl- hexyl) phenyl70yk10hexanol (660 mg, 4.68 mmol). Melting point 445- 444 ° C (after recrystallization from pentane).

Ia; (cnclš) 5656, 5590, 1651, 1616 and 1580 cn "“.

Ms; n / e 504 (M +), 286, 255 and 215.

(Hans: 504.2419 (czonšzoa). cis-((1,4,4-dimethylnonyl) -2-hydroxyphenyl] cyclohexanol (4.0 g, 400%) from cis-5-Albenzyloxy-4- (4,4-dimethylanyl) phenyl] cyclohexanol (5.0 g, 4.45 mmol). Melting point 82-85 ° C (after krist. and pentane). - IR: (CHCl 3) 5650, 5590, 1657 and 1597 cm -1.

Ms; n / e 546 (M *), 528, 255.and 215. _ Analysis -% C% H calculated for c25H¿802 '79, 71 11.05 79.71 11.14 found 10 15 20 50 40 7809060-2 49 transf5f [41 (1,1-dimethylnonyl) -2-hydroxyphenyl] cyclo hexanol (709 mg, 89%) from trans-5-β-benzyloxy-4- (1,1-di- methylnonyl) phenyl 17-cyclohexanol (1.00 g, 229 mmol). Melting point 69-70 ° C (after recrystallization from pentane).

IR: (OHH15) 5656, 5415, 1651, 1616 and 1562 cm -1.

Ms: m / 6 546 (M *), 526, 255 and 215.

Analysis ~% C% H calculated for C 15 H 58 O 2 79.71 11.05 found 79.11 10.86 cis-5- [4 (1,1-dimethyldecyl) -2-hydroxyphenyl] cyclo- hexanol (2.0 g, 98%) from cis-5-benzyloxy-4 + (1,1-dimethyl) decyl) phenyl70yk10hexanol (2.6 g, 5.78 mmol). Melting point 95- 94 ° C (after encircling in pentane).

IR; (0Hc1-) 5656, 5590, 1629 and 1567 cm

Ms; m / 6 560 (M +), 542, 266, 255 and 215.

Analysis ~% C% H calculated 79194 11.18 found 80,120 11.59 transf51? 4? (1,1-dimethyldecyl) -2-hydroxyphenyl; 7-cyclo- hexanol (150 mg, 45%) from trans-5'-benzyloxy-4- (1,1-dimethyl- decyl) phenyl7cyclohexanol (560 mg, 0.80 mmol). Melting point 76- 77 ° C.

IR: (CHCl 3) 5656, 5425, 1651, 1616 and 1560 cm -1.

Ms; m / 6 560 (M +), 542, 255 and 215.

Analysis -% C% H calculated for C 24 H 50 O 2 79.94 11.18 found 80.20 11.27 cis-5-yl (1,1-dimethylundecyl) -2-hydroxyphenyl; hexanol (2.59 g, 85%) from cis-5-Albenzyloxy-4- (1,1-dimethyl- undecyl) phenyl; 7cyclohexanol (5.5 g, 7.54 mmol). Melting point 65-66 ° C.

IR; , (OHH1) 5656, 5590, 1654 and 1592 cm

Ms: m / 6 574 (M +>, 556, 255 and 215.

Analysis -% C% H calculated for C 25 H 42 O 2 80.15 11.50 found 80.00 11.48 trans-β4 (1,1-dimethylundecyl) -2-hydroxyphenyl] cyclo- hexanol (487 mg, 60%) from trans-5-β-benzyloxy-4- (1,1-dimethyl- undecyl) phenyl7byclohexanol (1.00 g, 2.16 mmol). Melting point 75 ~ 74 ° C- 45 25 50 55 , 4o 9G 10-2 5o nu '(01:01,) 5656, 5445, 4657 and 4585 emil. ms; m / e 574 (M +), 556, 255 and 245.

Analysis -% C% H calculated for c25Hu2o2 80.45 44.50 found - ~ so, 44 44.46 cis-5-α (4,4-dimethylheptyl) -2-hydroxyphenyl octanol (0.795 g, 75%) from cis-5-ethylbenzyloxy-4- (4,4-dimethyl- heptyl) phenyl] cyclooctanol (4.56 g, 5.44 mmol). Melting point 89-90 ° C (after recrystallization from pentane). ' Ms: m / e 546 (M +), 528, 264 and 245.7 Analysis -% C% H calculated for c25H58o2 79.74 44.05 found 79.90 40.89 transf5-β4 (4,4-methylneptyl) -2-hydroxyphenyl; octanoy (2.62 g, 85%) from trans-5-ethylbenzyloxy-4- (4,4-dimethyl- heptyl) phenyl7cyclooctanol (4.0 g, 9.47 mmol). Melting point 76- 77 ° C (after recrystallization from pentane). 5 Ms; m / e 546 (rf), 528, 264 and 245.

Analysis -% C% H calculated for c25H58o2 79.74 44.05 found 79.84 40.86 Example §: Aliphenylbenzyloxy-4- (4,4-dimethylheptyl) -phenyl] cyclohex = 2- A solution of 5.89 g (40 mmol) of 2- (5-benzyloxy-4-bromo- phenyl) -2-methyloctane 40 ml of tetrahydrofuran were added slowly to 560 mg (44.4 mmol) of magnesium metal powder with a particle size size of 0.477-0.240 mm. The mixture thus obtained was boiled under reflux for 50 minutes and then cooled to 0 ° C.

To the solution was slowly added a solution of 4.40 g (40 mmol) 5-ethoxy-2-cyclohexen-4-one in 5 ml of tetrahydrofuran. Reactional The mixture was stirred for 50 minutes at 0 ° C and the reaction was quenched. was then broken up by adding 20 ml of 4N> H 2 SO 4 and heating on a steam bath for 50 minutes. The reaction mixture was then cooled and added to 200 ml of ether and 200 ml of water.

The organic extract was first washed with 200 ml of saturated sodium bicarbonate solution and then with 200 ml of saturated sodium chloride solution, dried over magnesium sulphate and evaporated, whereby an oil was obtained as the evaporation residue. Raw- the product was purified by column chromatography on 470 g 10 20 25 §O 55 7809000- BD 51 silica gel and elution were performed with ether pentane 1: 1.

2.5 U (54%) of the title compound were obtained as an oil.

IR: (CHCl 3) 1667, 1610 and 1556 6 m -1.

Ms; m / 6 404 (M +), 519, 515 and 91.

In the same way, §; [Élbens11oxy-4-§1,1-di- methylheptyl) -phenyl17 4-methylcyclohex + 2-enone in the form of an oil (4.12 g, 77%) using 5-ethoxy-6-methyl-2-cyclohexene 1-one (1.98 g, 12.9 mmol), magnesium (0.61 g, 25.7 mmol) and 12.9 mmol (5.0 g) of 2- (5-benzyloxy-4-bromophenyl) -2-methyloctane. '1R = (oHc1) 1667, 1615 and 1565 6m "". ns = m / 6 416 (M *), 400, 565, 555, 527, 299, 291 and 91.

Example 6: benzylbenzyloxy-4- (1,1-dimethyl-heptyl) phenyl7-5-methyl- cyclohexanone. To a solution of 4.17 mmol of dimethyl copper lithium in 10 ml of tetrahydrofuran, which solution had a tem ~ temperature between -10 ° C and -5 ° C, 5.60 mg (1.59) was added slowly mmol) 5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl] cyclohex-2- enone in 5 ml of tetrahydrofuran. The reaction mixture was stirred in another 50 minutes, after which the reaction was stopped by the reaction mixture was added to 100 ml of a saturated ammonium chloride solution and 100 ml of ether. After stirring for 10 minutes extraction was performed with 200 ml of ether. The ether extract washes was taken with 100 ml of a saturated sodium chloride solution, dried over magnesium sulphate and evaporated, thereby evaporating evaporation residue received an oil. This was purified by pre- parative layer chromatography on three silica gel plates 20 x 20 x 0.2 cm and elution was performed with cyclohexane ether 2: 1. Yield 282 mg (48%) (higher Rf) of the title compound in in the form of an oil and 211 mg (56%) (lower Rf) 5 ~ ¿É ¥ benzyloxy- 4- (1,1-Dimethylheptyl) phenyl] 1-methylcyclohex-2-ene-1-O1 in the form of an oil.

Category Association: IR: (0601) 1704, 1610, 1565 cm -1.

Ms; m / 6,420 (M +), 405, 577, 555 and 529. §; β-Benzyloxy-4- (1,1-dimethylheptyl) phenyl] -1-methylcyclohexyl- 2-en-1-ol: IR: (CHCl 3) 5571, 5401, 1661, 1608 and 1585 cm -1.

Ms: m / 6 420 (M *), 402, 555 and 517. 10 15 20 50 55 52 Example 7: 5- [α- (1,1-dimethylheptyl) -2-hydroxyphagylybyclohex-2-enone A mixture of 400 mg (0.988 mmol) of 5-β-benzyloxy-4-7 (1,1-dimethylheptyl) phenyl] cyclohexa2-enone and 20 mg of a lysator consisting of 5% palladium-on-carbon was stirred under hydrogen with a pressure of 1 atmosphere for 50 minutes. The reaction mixture was then filtered through diatomaceous earth with ether and the filtrate evaporated. The solid crude product thus obtained is recrystallized. read in petroleum ether to give 110 mg (55 ffs) of the title compound, mp 122-125 ° C. la; (rar) 5448, 1654, 1608 and 1565 6m '“. las; m / e 514 (lf), 299 and 229.

Analysis ~% C% H calculated for C 21 H 50 O 2 80.21 9.62 found 80.25 9.46 Example 8: 5- (2,4-Dihydroxyphenyl) cyclohexanone methyl ketal. To one solution of 7.0 g (55.0 mmol) of 5- (2,4-dihydroxyphenyl) cyclohexanone in 100 ml of methanol and 15 ml of trimethyl orthoformate, which solution had a temperature of G ° C, 10 drops were concentrated the sulfuric acid and the reaction mixture were stirred for 5 hours without cooling, whereby the temperature was allowed to rise to room temperature.

-Then the reaction was stopped by adding solid sodium bicarbonate. lived in excess. The reaction mixture was evaporated under reduced pressure and the residue was dissolved in 200 ml of water-250 ml ether. The ether extract was washed once with 150 ml of saturated sodium hydroxide solution. bicarbonate solution, dried over magnesium sulphate and evaporated, whereby an oily evaporation was obtained. which crystallized from ether-pentane. Nan received 5.74 g (77%) of the title compound, m.p. 129-150 ° C. nu (Klar) 5289, 1629, 1615 .och 1597 em ”. ns: 220 (rf), 205, 205, 188, 177, 161 and 156 ..

Analysis -% 0% H calculated for '045111605 70.89 7.52 found 70.79 7.54 Example 9: 5-N-hydroxy-4- (4-phenylbutyloxy) phenyl] cyclohexanone methyl ketal. A mixture of 5.05 g (22.8 mmol) of 5- (2,4-di- hydroxyphenyl) cyclohexanone methyl ketal, 10.1 g (75.2 mmol) 10 45 50 55 55 anhydrous potassium carbonate and 6.12 g (26.8 mmol) of 4-phenyl- butyl methanesulfonate in 25 ml of N, N-dimethylformamide was heated at 85-100 ° C for 4 hours. The reaction mixture was cooled and was added to 200 ml of water-200 ml of ether. The ether extract was washed with water Q x: 200 ml), dried over magnesium sulphate and evaporated to give an oil. This was purified by column chromatography on H00 g silica gel and elution was performed with pentane ether 2: 1. 7.4 δ (92%) of the title compound in the form of an oil.

IR; (0H015) 1625 ooh 1590 om ”.

Ms; m / o 552 (If) ooh 91.

Analysis -% C% H calculated for C 25 H 28 O 5 78.57 8.01 found 78.54 8.07 The following compounds were prepared in the same manner but with use of suitable mesylate derivatives instead of 4 butyl methanesulfonate 5-Hydroxy-4- (2-heptyloxy) phenylpheyclohexanone methyl ketyl (6.45 g, 75%) as an oil from 5.7 g (25.9 mmol) of 5- (2,4- dihydroxyphenyl) cyclohexanone methyl ketal and (2-heptyl) methanesulphate phonate (6.2 g, 52.5 mmol).

IR; (0H015) 1657 ooh 1600 om ”.

Ms; m / o 518 (W), 286, 274, 220, 204 ooh 178. Hydroxy-4- (2-octyloxy) phenylybyclohexanone methyl ketal in the form of an oil (5.05 g, 58%) of 5- (2,4-dihydroxyphenyl) - cyclohexanone methyl ketal (5.7 g, 25.9 mmol) and (2-octyl) methane sulfonate (7.5 g, 55.1 mmol).

IR: (c fi clš) 1659 ooh 1600 om ”.

Ms = m / o 552 (If), 500, 269, 272 ooh 220. Hydroxy-4- (2-nonyloxyphenyl] cyclohexanone methyl ketal (5.25 g, 59%) as an oil of 5 - (2,4-dihydroxyphenyl) - cyclohexanone methyl ketal (5.7 g, 25.9 mmol) and (2-nonyl) methane sulfonate (7.9 g, 55.5 mmol).

IR; (01101) 1654 ooh 1590 om ”.

Ms; m / o 546 01+). 514. 220, 168 ooh 161. Hydroxy-4- (2- (4-phenyl) butoxy) phenylybyclohexanone methyl ketal as an oil (5.1 g, 56%) of 5- (2,4-dihydroxy phenyl) cyclohexanone methyl ketal (5.7 g, 25.9 mmol) and 2- (4- phenylbutyl) methanesulfonate (8.0 g, 55.0 mol). 10 15 20 50 55 54 IR: (cnclš) 4659 and 4605 6n ''.

MS: m / e 552 (HT), 520, 220 and 188 ,. Hydroxy-4- (2- (6-phenyl) hegyloxy) phenyl] cyclohexanone- methyl ketal (5.5 g, 54%) as an oil of 5- (2,4-dihydroxy) phenyl) cyclohexanone methyl ketal (5.7 g, 25.9 mol) and 2- (6- phenylhexyl) methanesulfonate (9.0 g, 55.5 mmol).

IR; (cHc15) '4654 and 459? 6nf “.

M6; n / 6 58o, 2542 (M +, c 25 H 52 O 5), 22o, 4o88; 488, o986 and 1773550- 5 6 - Example 10: 57β-hydroxy-4- (4-phenylbutyloxy) phenylylcyclohexanone.

A mixture of 6.8 g (49.5 mmol) of 5-β2HydroXi-4- (4- phenylbutyloxy) phenylybyclohexanone methyl ketal, 100 ml 2N-H01 and 60 ml of dioxane were heated at reflux for 1 hour hour. The reaction mixture was cooled and added to 500 ml of ether 500 ml saturated sodium chloride solution. The ether extract was washed 1 once with 500 ml of a saturated sodium chloride solution and then Once with 500 ml of a saturated sodium bicarbonate solution, dry was added over magnesium sulphate and evaporated to an oil. This was purified by column chromatography on 400 g of silica gel and elution was performed with ether cyclohexane 1: 1. Yield 6.4 g (98%) of the title compound as an oil.

IR: (QHG15) 5574, 5555, 4748 (weak), 4626 and 4595 cnfq. ns: n / 6 588 (M *), 520, 540, 295, 268 and 94. The following compounds were prepared in the same manner from ketals according to Example 9: 5γ (2-heptyloxy) -2-hydroxyphenyl7-cyclohexane * (4.7 g, 82%) as an oil from 6.0 g (18.8 mmol) of the corresponding The methyl ketal. "1 IR: (CHCl) 5656, 5590, 1724 (weak), 1659 and 1600 cm ns = n / 6 504 (M *), 206, 488, 474, 465 and 457. 57? [(2-octyloxy) -2-hydroxyphenyl] cyclohexanone (4.1 g, 85%) as an oil from 5.0 g (15.0 mmol) of the corresponding methyl ketal. in: (cHc15) 5656, 5378, 4724 (weak), 4654 and 4595 6n ''. ns; n / 6 548 (rf), 206, 488, 478 and 465. 5- [9- (2-nonyloxy) -2-hydroxyphenyl] cyclohexanone (4.55 g, 89%) in the form of an oil from 5.1 g (14.7 mmol) of the corresponding methyl ketal. 40 45 55 IR = (011015) 5564, 5567, 1709 (weak), 1626 and 1567 if ". m / e 552 (vf), 206, 107 and 171. (1- (2- (4-phenyl) butyloxy) -2-hydroxyphenyl] cyclohexanone (5.8 g, 79%) from 5.0 g (14.2 mmol) of the corresponding methyl ketal in the form of an oil.

IR: (CHCÄ) 5636, §425, 4724 (weak), 4657 and 4600 cm_q. ms; m / e 556 (rf), 206, 186, 152, 117 and 91. (2- (6-phenyl) hexyloxy) -2-hydroxyphenylycyclohexanone (4.45 g, 89%) as an oil from 5.2 g (15.6 mmol) of it corresponding to the methyl ketal.

IR: (CHCl5) §6§6, §} 90, 1748, 46§7 OCh 4600 cm_q.

Ms: m / e 566 (IF), 206, 166 and 91.

Example 11: cis-5-Alhydroxy-4- (4-phenylbutyloxy) phenyl] cyclohexanol and the trans isomer. To a solution of 4.8 g (14.2 mmol) of 5-ÅÉÄ hydroxy-4- (4-phenylbutyloxy) phenylcyclohexanone in 25 ml of methanol, which solution had a temperature of -18 ° C, 0.559 g was added (14.2 mmol) sodium borohydride. The reaction mixture was stirred in 40 minutes and then added to 250 ml of saturated sodium chloride solution-250 ml of ether. The ether extract was washed once with 150 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated to an oil. This was purified by column chromatography on 400 g of silica gel and elution was carried out with dichloromethane ether 2.5: 4 to give 5.57 g (70%) of the cis isomer, which was recrystallized from cyclohexane, and 0.68 g (14%) of the trans isomer, which was crystallized from cyclohexane and 0.69 g (14%) was mixed material. cis isomers: Melting point 79-80 ° C.

PM: δ 2.70 (m, benzylic methylene), 5.26 (m, benzylic methine), 5.95 (bt, J = 6Hz, -OCHÉ-), 4.28 (m, OH, carbinolmethine, with D 2 O 04.25, M, carbinolmethine), 6.42 (dd, J = 8 and 2Hz, ArH), 6.45 (d, J = 2Hz, ArH), 7.05 (d, J = 8Hz, ÅrH) and 7.22 (s, PhH).

IR; (0H015) 5610, 5555, 1651 and 1605 if '.

Ms: m / e 540 (W), 522, 190 and 91.

Analysis -% C% H calculated for C22H2805 77.64 8.29 found 77.46 8.25 10 15 20 25 50 55 56 trans isomers: m.p. 112-114 ° C.

Pmh = 6g% el 2.68 (m, hcncylish mccylch), 5.80 (m, oh, -OCH 2 -, carbinolmethine, with D 2 O 65.65, m, carbinolmethine and 65.90, bh, J = 6Hz, -CCH 2 -), 6.52 (bs, overlaps 86.40), 6.40 (da, J = 8 and 2Hz, Arh), 7.00 (0, J = 8Hz, Arn) and 7.20 (S, Phh).

IR; (0H01¿) 5610, 5590, 1651 cch 1595 cm '“. ms: m / c 540 (M +), 522, 190 and 91.

Analysis -% 0% H calculated for C22Ha805 77.61 8.29 found 77.40 8.51 In the same way the following compounds were prepared: cis-5-ÅÄÄ (2-heptyloxy) -2-hydroxyphenylycyclohexanol and the trans isomer in the form of oils from 5- 4- (2-heptyloxy) hydroxyphenylycyclohexanone (5.2 g, 15.6 mmol). Ur kíse1dioxide ~ gel was first eluted with 854 mg (56%) of the cis-5 isomer and 107 mg (5%) of the trans-5 isomer. 2iâ = : h = (0801) 5597, 5555, 1629 cch 1600 cm '“. ms; m / c 506 (M +, 208, 190, 175 and 162).

PNB: ÖTMS 0.82 (m, methyl), 2.8 (m, benzylic methine), 0CDCl5 5.7 (m, carbinolmethine and OH), 4.1 (m, methine), 6.58 (m, ArH) , cch 6.95 (0, J = 8Hz, Arh). Éåâšš * Ms; m / c 506 (hf), 208 cch 190.

PMh = cggålš 0.82 (m, mctyl), 5.25 (m, hcnsylish mccin), 4.5 (m, harhinclinchin and OH), 6.55 (m, ArH) and 6.94 (0. J = 8Hz, Ar fi). cis-5-α> (2-ethylcoxy) -2-hydroxyphycylcycline and the trans isomer of 5- [Al (2-octyloxy) -2-hydroxyphenyl] cyclo- hexanone (2.92 g, 9.18 mmol). By elution from silica gel 1.58 g (54%) of the cisF5 isomer was obtained first and then 0.57 g (19%) of the trans-5 isomer. ggâz IR: (CHCl5) 5665, 5590, 165? And 1608 Om-4. hs = m / c 520 (M +), 519, 208 and 190. hmm: cgšâl 0.85 (m, mchyl), 2.81 (m, hchcylich mchin>, 5.8 (m, carbinolmethine), 4.1 (m, side chain methine and OH), 6.55 (m, ArH) and 6.96 (d, J = 8Hz, ArH). \ i1 10 15 55 40 57 EÉÉQÉ: In: Ms; m / 6 520 (M +), 255, 206, 190 and 175.

PMR: δ δ 0.82 (m, methyl), 5.25 (m, benzylic methine), 4.1 ~ 4.9 (m, carbinol and side chain methin and OH), 6.55 (m, Arn) and 6.96 (6.j = 6Hz, Ara). cis-5-14 [(2-nonyloxy) -2-hydroxyphenyl] cyclohexanol and the trans isomer of 5- [Al (2-nonyloxy) -2-hydroxyphenyl] cyclo- hexanone (51.5 g, 19.48 mmol). By elution from silica gel 2.11 g (67%) of the cis-5 isomer were obtained first and then 0.52 g (10%) of the trans-5-isomer as oils. gišz IR; 7 (0H015) 5665, 5590, 1659 and 1610 6mf “.

Ms; m / 6 554 (M *), 516, 206 and 190.

PNB; agšâlä 0.66 (m, methyl), 2.65 (m, benzylic methine), 5.5-4.1 (m, carbinolmethine and OH), 4.22 (m, side chain methine), 6.58 (m, ArH) and 6.9? (d, J = 8Hz, ArH). Éåêëâï IR: (CHCl 3) 5656, 5415, 1657 and 1592 cm -1. ns; 6/6 554 (rf), 516, 206, 206 and 190.

P66; cggål 0.66 (m, mephyl), 5.25 (m, benzylic methine), 5.9-4.6 (m, carbinol and side chain methines and OH), 6.56 (m, _ArH) and 6.96 (d, J = 8Hz, Ar fl). » cis-5-14? (2- (4-phenyl) butyloxy) -2-hydroxyphenyl] cyclo- hexanol and the trans isomer of 5- [N (2- (4-phenyl) butyloxy) -2- hydroxyphenylgyclohexanone (2.9 g, 8.25 mmol). Upon elution from silica gel, 1.29 g (44%) of the cis-5 isomer was first obtained and then 241 mg (8%) of the trans-5 isomer. giâz Melting point 96 ~ 105 ° C (after recrystallization from pentane).

IR; (cH015) 5656, 5590, 1654 and 1606 6m "".

M6; m / 6 540 (M +), 522, 206, 190, 162, 147, 156 and 91.

PM6 = 6§% â1 1.50 (6, J = 6Hz, methyl), 5.75 (m, carbinol- methine), 4.25 (m, side chain methine), 6.21 (d, J = 2Hz, ArH), 6.58 (da, J = 6 and 2Hz, ArH), 6.96 (6, J = 6Hz, Ar fl) and 7.20 (S, Fn).

Analysis ~% C% H calculated for C 22 H 28 O 5 77.61 8.29 found 77.59 8.18 trans: 1 IR: (CHCl 5) 5625, 5590, 1657 and 1595 cm -1. 40 45 20 25 50 i "'\ -....- and side chain methines), 6.57 (m, Ar fl), 6.95 (d, 58 Ms; m / e 540 (rf), 542, 206, 490, 462, 447, 456 and 94.

Pm; aäšscl 4.50 (a, J = 6Hz, memory), 5.5 (m, bemsylic methine), 4.25 (m, carbinol and side chain methines), 6.58 (m, Arn), 6.94 (d, J = 6Hz, Arm and 7.46 (s, Pm). 615-514424s-femynememlomi) -z-neutroxymvycyclo- hexanol and the trans isomer of 5-α (2- (6-phenyl) hexyloxy) -2- hydroxyphenyl7-cyclohexanol (5.5 g, 9.04 mmol). Upon elution from silica gel, 4.54 g (46%) of cis-5-iso- and then 274 mg (8%) of ÜranS-5-íSóm6ren- CIS: smäimpmmkm: 99-445 ° c (after omlmism. in pemmam). m; (0601) 5656, 5567, 4654 661m 4592 6m "'. ns: m / e 566 (M +), 550, 206, 490, 462, 447, 456 and 94.

Pm; loop 4.50 (a, J = 6Hz, methyl), 5.6 (m, carbimol methine), 4.2 (m, side chain methine), 6.57 (m, ArH), 6.98 (d, J = 8Hz, ArH) and 7.48 (s, PhH).

Analysis -% 0 “96 H calculated for 024115205 76.22 6.75 room 76.05 6.56 Rails; in; (06015) 5656, 5445, 4654 and 4597 cm ”. 5 ms: m / e 566 (rf), 550, 206, 490, 462, 447, 456 and 94.

PMR: δ 4.25 (α, J = 6Hz, memyl), 4.24 (m, cambimol J = 6Hz, AmH) and 7.45 (s, PhH).

Example 42: 5β (4,4-dimethylheptyl) -2-hydroxyphenyl] -2-cyclohexenol.

To a solution of 4.00 g (5.48 mmol) of 5-α (4,4-dimethyl) heptyl) -2-hydroxyphenyl 17-2-cyclohexenone in 60 ml of ether, which solution had a temperature of -50 ° C, 6.5 ml was added dropwise of a 4 molar solution of diisobutylaluminum hydride in toluene.

The reaction mixture was stirred for an additional 50 minutes at -50 ° C and then added to 4.5 l of water, whereby the reaction was suspended. Then extraction was performed with ether (5 X 400 ml) and the combined ether extracts were washed with a saturated solution of sodium chloride (2 x 425 ml) and dried over magnesium sulfate. After evaporation, the crude product was purified by column chromatography on 50 g FIORIAI, whereupon recovered an oil by eluting with ether. The oil crystallized 40 15 20 25 50 55 40 7309060-2 59 from pentane to give 256 mg (25%) of the title compound.

Melting point 87-88 ° C.

MS: m / e 516 (M +), 298, 251 and 243.

Analysis -% C% H calculated for C 21 H 52 O 2 79.70 40.49 fllnnêt 79, 58, 96 Example 15: 2- [α- (4,4-dimethylheptyl) -2-hydroxyphenyl] -5-cyclohexenone etzlenketal. A solution of 500 mg (1.59 mmol) of 5-β (1,1-dimethyl- heptyl) + 2-hydroxyphenyl7-2-cyclohexenone, 7.8 g (127 mmol) of ethylene glycol, 575 mg (5.18 mmol) hydroquinone and 50 mg (0.265 mmol) p-toluenesulfonic acid monohydrate in 50 ml of benzene was heated at reflux temperature for 12 hours using a condenser densor according to Dean-Stark filled with molecular sieves 5A. Reactional the mixture was cooled and added to 500 ml of a saturated sodium bicarbonate solution, whereby the reaction was stopped. Then ext- the reaction mixture was reacted with ether (5 x 150 ml), the resulting The combined extracts were dried over magnesium sulphate and evaporated. to a solid evaporation residue. This was purified with help by column chromatography on 50 g of silica gel. Elution was carried out with 50% ether-petroleum ether to give (after omkrist. in pentane) 595 mg (69%) of the title compound. Melting point 97-98 ° C.

MS: m / e 558 (M &lt; + &gt;), 297, 275, 245 and 225.

Analysis - 5% C% H calculated for C25H54O5 _ 77.05 9.56 found 76.98 9.42 Example 14: 2- [N- (1,4-dimethylheptyl) -2-hydroxyphenyl] N-4-methylcyclo- hex-5-enone. A mixture of 4.08 g (0.4 mol) of 5-α- (fi, 4-di- methylheptyl) -2-hydroxyphenylph-4-methyl-cyclohex-5-enone-ethylene- ketal, 50 ml of 2-normal oxalic acid and 50 ml of methanol were stirred at 25 ° C for 6 hours. The reaction mixture was added to 500 ml water - 250 ml of ether. The ether extract was washed once with 250 ml of a saturated sodium bicarbonate solution, once with 250 ml of a saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The evaporation residue was purified using column chromatography on 400 g of silica gel and elution was carried out with 50% ether-pentane to give the title Association. vseäntßeæ 40 '15 20 25 50 55 60 Example 45: (7,4-dimethylheptyl) -2-hydroxyphenyl; 7Cyclohex + 5- en-4-ol. To a solution of 17.5 g (50 mmbl) 5 “ÅÃ; (1,1-dir methylheptyl) -2-hydroxyphenyl7-cyclohex-5-enone in 50 ml of methanol, which solution had a temperature of -18 ° C, was added ¶.9 g (50 g) mmol) sodium borohydride. The reaction mixture was stirred for 30 h minutes and then added to 250 ml of a saturated sodium chloride solution-250 ml of ether. The ether extract was washed once with 250 ml of a saturated sodium chloride solution, dried over magnesium sulfate and evaporated. The evaporation residue was purified by column chromatography on 400 g of silica gel and elution was performed with 5096 ether-pentane, whereby one received the headline association.

Example 16: Acyl (1,1-dimethylheptyl) -2-hydroxyphenyl7-Cyclohex + 2- en-4-01. To a solution of 70 ° C (0.2 ° m01) 5-β methylheptyl) -2-hydroxyphenylphicyclohex-2-enone in 200 ml of methanol, which solution had a temperature of -18 ° C, 7.6 g was added (0.20 mol) sodium borohydride. The reaction mixture was stirred for 50 minutes and then added to 1 liter of a saturated sodium chloride solution-'l 1 ether. The ether extract was washed in groups with 500 ml of a saturated sodium chloride solution, dried over magnesium sulphate and evaporated. The evaporation residue was purified by column chromatography on 500 g of silica gel and elution was performed with 50% ether-pentane, thereby received the headline association.

Example 47: _ » Acetoxy (4- (4,1-dimethylheptyl) phenyl] cyclohexanone.

A solution of 2.0 g of 5-hydroxy-4- (1,1-methylheptyl) phenyl] cyclohexanone in 45 ml of pyridine was treated at 10 ° C with 10 ml acetic anhydride and the mixture was stirred for 48 hours nitrogen. It was then poured onto ice / water and acidified dilute hydrochloric acid. The acidified mixture was extracted with ethyl acetate (2.x400 ml), the extracts were combined, washed with salt Mkning and dried over MgSO4l By evaporation under reduced pressure, the title compound was obtained in the form of a Oil.

V1 40 15 25 55 40 Example 48: 4-acetoxy-5- [Elacetoxy-4- (2- (5-phenyl) pentyloxy) phenylZ; 9ï5lghg¿âg._To a solution of 2.0 g of 5-¿É ¥ hydroxy-4- (2- (5- phenyl) -pentyloxy) phenyl7byclohexanol oil in 20 ml of pyridine was added at 40 ° C 20 ml of acetic anhydride and the mixture was stirred under nitrogen for 48 hours. It was then poured onto ice / water and acidified with dilute hydrochloric acid. The product was isolated by extraction with ethyl acetate (2 x 400 ml). They combined the extracts were washed with brine, dried over MgSO 4 and evaporated to give the diacetyl derivative in shape of an oil.

Example 49: 5712 (4-Morpholinobutyryloxy) -4- (4,4-dimethylheptylphenyl) cyclohexanol. Dicyclohexylcarbodiimide (0.227 g, 4.4 mmol) and 4-N-Piperidyl-butyric acid hydrochloride (0.22 g, 4.0 mmol) was added to a solution of 5-β-alhyaroxy-441, fl-dimethylheptyl) phenyl cyclohexanone (0.500 g, 4.0 mmol) in methylene chloride (25 mL) at room temperature. The mixture was stirred for 48 hours and cooled then to 0 ° C, filtered and the filtrate evaporated, through was obtained the title compound in the form of its hydrochloride ..

Example 20: fi polyhydroxy-4- (4,4-dimethylheptyl) phenyl] 44-methylene- 'cyclohexane. To 50% sodium hydride / mineral oil (2.28 g, _48 mmol) washed in pentane (5 x 25 ml) was added 90 ml of dry methyl sulfoxide and the mixture was heated at 70 ° C for 0.75 hours. Then 47.79 g (54 mmol) were added at once methyltriphenylphosphonium bromide. The yellow solution was stirred in 50 minutes at 25 ° C, then 2.26 g (6.5 mmol) of 5-β-acetoxy-4- (1,4-dimethylheptyl) phenyl; 7-cyclohexanone dissolved in 90 ml of dimethyl- sulfoxide was added all at once and the mixture was heated at 65-65 ° C for an additional 4.5 hours. The reaction mixture was poured into 450 ml of ice water / 25 g of NaHCO 5 and extracted with ether (5 x 50 ml). The combined ether extracts were dried over NgSO 4, decolorized with charcoal and filtered through a bed of silica gel, whereby a colorless oil was obtained, which chromatographed on 75 g of silica gel. Elution through carried with cyclohexane. First, a non-polar contaminant was eluted, whereupon the polarity of the solvent was increased to ether / cyclohexane (4:40), whereby the title compound was obtained in the form of a colorless oil. 'ca v. g CD 1 ..) _ 10 45 50 55 hay Example 21: - hydroxyhydro-4- (1,1-dimethylheptyl) phenyl] 11-hydroxy- methylcyclohexane. A solution of 1.05 g of s- [α-hyaroxy-α- (wa- dimethylheptyl) phenyl711-methylenecyclohexane (5 mmol) in 25 ml dry hetrahydrofuran is dissolved at 0 ° C in an ice / water bath.

Borane-tetrahydrofuran complex (4.5 mL, 4.5 mmol, 1-molar solution) was added and the colorless solution was stirred whole overnight at room temperature (18 hours). The mixture is cooled in ice and 8 ml of water were added to decompose excess on reagent. The whole was stirred for 15 minutes, then 5 ml (9 mmol) of a 5-normal solution of sodium acetate and then 5 ml of 50% hydrogen peroxide was added. The reaction mixture was stirred at 0 ° C for 15 minutes, after which its temperature was allowed to rise to room temperature. peraturen. Stirring was continued overnight (24 hours).

The reaction mixture was poured into 100 ml of ice water and extracted then with ether (5 x 50). The combined ether extracts are was taken with sodium sulfite to adversely reactive starch reaction, dried over MgSO 4 and evaporated to dryness, whereby a pale yellow oil was obtained, which was chromatographed on 50 g silica gel. Cyclohexane / ether 5: 1 and the product was obtained as a colorless foam.

Example 222 erans-4 -_ / _. '2'-benzyloxy-4- (1,1-dimethylheptyl) ~ f @ y¿7¿§¿ buten-2-one. A solution of 2-benzyloxy-4- (1,1-dimethylheptyl) - benzaldehyde (65.2 g, 0.195 mol) and 1-triphenylphosphoranylidene 2-propanone (62.0 g, 0.195 mol) in dichloromethane (195 ml) heated at the reflux temperature for 20 hours. Another serving of 15.5 g of ylid_ (15.5 g, 0.047 mol) was added and the heating at reflux temperature was continued for 24 hours. Reactional the mixture was cooled, evaporated, and diluted with ether. The formed the precipitate of triphenylphosphine oxide was filtered off. The the crude oil was purified by column chromatography on 1.5 kg of silica dioxide gel. Elution was performed with 20% ether-hexane and man obtained 55.9 g (74%) of the title compound as an oil.

IR; (csci) 1681, 1621 and 1575 cm ”.

Ms = (m / e) 578 01+), 564. 557, 295, 271, 251 and 91.

Example 25: Cylbenzyloxy-4- (1,1-dimethylheptyl) phenyl] 4-carbomethoxy- 1,5-cyclohexanedione. To a solution of sodium methoxide (0.67 g, 10 15 20 25 50 73Û9Û6Ü-2 65 42.4 mmol) and dimethyl malonate (1.86 g, 14.4 mmol) in methanol (4.75 ml) was slowly added a solution of trans-4- [Albenzyloxy- 4- (4,4-dimethylheptyl) phenylyls-buten-2-one (5.5 g, 9.92 mmol) in methanol (4 ml). The reaction mixture was heated at room temperature. the flow temperature for 5 hours, after which it was cooled and evaporated. under reduced pressure. The residue was diluted with ether and a saturated sodium chloride solution and the whole was acidified with 4N-H01. The ether extract was washed with a saturated solution of sodium chloride (2 x 500 ml), dried over magnesium sulphate and evaporated to give 4.71 g (99%) of the title compound with a melting point of 108 ~ 409 ° C (after recrystallization in petroleum ether-ether).

Ia = cnci 1742, 1709, 1642 and 157? em "".

Ms »(m / e) we (MW. 446. 419, 595, ss? Och 9”.

Analysis ~% C% H calculated for C5OH58O5 § 7, 28 8.00 found 75.05 7.97 Example 24: 5β-benzyloxy-4- (1,4-dimethylheptyl) phenyl] 4,5-cyclo- hexandion. A mixture of 5-Zilbenzyloxy-4- (1,1-dimethyl- heptyl) -phenyl7-4-carbomethoxy-4,5-cyclohexanedione (20.8 g, 45.5 mmol), dioxane (40 ml) and 20% sodium hydroxide (40 ml) 0 was heated at 100 ° C for 2.5 hours, then cooled in one ice bath and acidified with concentrated hydrochloric acid. The mixture heated for 4 hours at 100 ° C, cooled to 0 ° C and neutralized. was mixed with sodium bicarbonate. The mixture thus obtained was added to saturated sodium bicarbonate and ether. The ether extract dried over magnesium sulphate and evaporated to an oil.

By purifying this oil by column chromatography on 4 kg of silica gel and elution with 10% acetone-ether were obtained 40.9 g (60%) of the title compound, m.p. 105 ° C (after recrystallization from pentane ether).

IR: (CHCl 5) 5656-2222 (brett), 1759, 1712, 4615 (brett) and 1577 (shoulder).

Ms: m / e 420 (n *), 555, 529 and 94.

Analysis -% C% H calculated for C 28 H 56 O 5 79.96 8.65 found 79.87 8.54 40 20 3 _64 Example 25: 5-α-Benzyloxy-4- (4,4-dimethylheptyl) phenyl] -5-methoxy-2- cyclohexsn-1-one. A solution of 5-ethylbenzyl-4- (1,1-methylethyl) heptyl) phenyg7L1,5-cyclohexanedione (5.0 g, 11.9 mmol) and p- toluenesulfonic acid (200 mg) in methanol (250 ml) in a flask connected to the one with a soxhlet condenser containing molecular sieves 5A heated at reflux temperature for 50 minutes. Reactional the mixture was cooled, concentrated under reduced pressure and the residue was diluted with a saturated sodium bicarbonate solution and ether. The ether extract was washed with a saturated sodium bicarbonate. bonate solution and then with a saturated sodium chloride solution, then dried over magnesium sulfate and evaporated. MAN obtained 5.45 U (99%) of the title compound as an oil.

IR; (OH1) 1644, 1612, 1505, 1460 and 1579 cm

Ms; (m / e) 454 (M +), 549, 545 and 91., Exemge1'2s = 5-α-benzyloxy-4- (4,4-dimethylheptyl) phenyl7-2-cyclohexene- 1:95. To a solution of the title compound of Example 25, i.e. 5-12-Benzyloxy-4- (4,4-dimethylheptyl) phenyl7-5-methoxy-2- cyclohexen-4-one (500 mg, 4.45 mmol) in ether (20 mL), which solution had a temperature of 0 ° C, lithium aluminum was added hydride (20 mg, 0.55 mmol). The reaction mixture was stirred in 50 minutes at 0 ° C, acidified with 4N-HO1 and stirred for 2 h 25 50 55 40 hours at room temperature. The ether phase was separated, washed with a saturated sodium bicarbonate solution and then with a saturated sodium chloride solution, after which it was dried over magnesium sulfate and evaporated. The crude oil was purified by column chromatography on 400 g of silica gel and elution by was carried out with 50% ether-pentane to give 555 mg (76%) of the title compound as an oil.

IR: (CHCl 3) 4684, 4672, 4645, 4575 and 4479 cm Ms; (m / e) 404- (mf), 519, 515 and 91.

Example 27: 5-12-Benzyloxy-4- (4,4-dimethylheptyl) phenyl7-5-methyl-2- cyclohexen-4-one. To a solution of methylmagnesium iodide (44 ml of a 2.9 molar solution in ether) and tetrahydrofuran (40 ml), which solution had a temperature of 0 ° C, was added dropwise a solution of 5-12-benzyloxy-4- (4,4-dimethylheptyl) - phenylyl5-methoxy-2-cyclohexen-4-one (5.45 g, 7.95 mmol) i tetrahydrofuran (40 ml). The reaction mixture was heated and 40 15 20 25 50 55 40 7809Û6Ü-2 65 was stirred at room temperature for 2 hours, then added to ice-cold 1N-HCl. After stirring for 20 minutes, it was extracted the hydrolysis mixture with ether. The ether extract was washed with a saturated sodium bicarbonate solution, then with a saturated sodium chloride solution, dried over magnesium sulphate and concentrated fumes. The crude product was purified by column chromatography on 100 g of silica gel and elution was performed with 25% ether-pentane. This gave 5.08 g (95%) of the title compound. the compound having a melting point of 60-61 ° C (after recrystallization in pentane. l Ms = (m / c) 418 (MH +, 555, 527 and 91).

In the same manner, the following compounds were prepared from Reagents: 5_-1-bicyclicyl-4- (1,1-acetylhylpytynyl) -5-ethyl-2- cyclohexen-1-one (2.85 g, 82%) as an oil from 5-12 benzyloxy-4- (1,1-dimethylheptyl) phenyl] -3-methoxy-2-cyclohexene- 4-one (5.46 g, 7.97 mmol) and 10.8 ml of 2.94 molar ethylmagnesium- bromide (in ether).

IR; (C801> 1698, 1666, 1625 and 1582 cnfl.

Ms: (m / c) 452 (MH, 541 and 91). 2-1E-benzyloxy-4- (4,1-dimethylheptyl) phenyl] -5-n-propyl- 2-cyclohexen-1-one (5.48 g, 85%) as an oil from 5-12 Benzyloxy-4- (1,4-dimethylheptyl) phenyl] -5-methoxy-2-cyclohexene- 1-one (4.00 g, 9.24 mmol) and n-propylmagnesium bromide (56.8 mmol).

IR: (cm) 1661, 1651, 1612 and 1575 cm -1.

Ms; (m / c) 446 (MÜ, 555 and 91). 2-12-benzyloxy-4- (4,1-dimethylheptyl) phenyl] -5-n-hexyl- 2-cyclohexen-1-one (4.11, 92%) as an oil from 5-12 Benzyloxy-4- (4,1-dimethylheptyl) phenyl] -5,5-methoxy-2-cyclohexene- 1-one (4.00 g, 9.24 mmol) and 7.57 mL of a 2.5 molar solution of n-hexylmagnesium bromide (in ether).

IR; (chci) 1678, 1661, 1655, 1618 and 1582 cm '.

Ms: -Qm / c) 488 (M +), 405, 59? cch 91.

Example 28: cis-5-1-Benzyloxy-4- (1,1-dimethylheptyl) -phenyl] metzl-cyclohexanone. A mixture of 5-1E-benzyloxy-4- (4,4- dimethylheptyl) phenyl] -5-methyl-2-cyclohexen-1-one (1.00 g, 2.59 mmol) and 500 mg of 5% palladium-on-carbon-50% water was stirred in hydrogen at a pressure of 4 atmospheres for 1 hour. A second 40 45 20 25 50 55 66 500 mg portion of catalyst was added and stirring continued for 50 minutes. A third dose of 500 mg lysator was added and stirring was continued for 45 minutes.

The reaction mixture was then filtered through sodium bicarbonate and magnesium sulfate and the filtrate was evaporated.

The evaporation residue was purified by column chromatography. 440 g of silica gel and elution were performed with 40% ether-petroleum ether. Nan received 525 mg (52%) of the title the compound in the form of an oil. ~ Ms: (m / e) 420 (M +), 402, 565, 355, 529 and 91.

Example 29: cis-5-Al (1,1-methylpheptyl) -2-hydroxyphenyl7L5-methyl- cyclohexanone. A mixture of 5-12-benzyloxy-4- (4,4-dimethyl- heptyl) phenyl7-5-methyl-2-cyclohexen-4-one (2.85 g, 6.77 mmol), 4.5 g of 5% palladium-on-carbon-50% water and sodium bicarbonate (2.8 g) in methanol (50 ml) was stirred in hydrogen with a pressure of 4 atmosphere for 45 minutes. The reaction mixture was filtered through diatomaceous earth and the filtrate was evaporated under reduced pressure print. The residue was dissolved in ether, the ether solution was dried with magnesium and evaporated. By recrystallization of The evaporation residue in pentane obtained 4.45 g (52%) of the title compound. the compound with a melting point of 95-98 ° C.

Analysis -% C% H8 calculated for C 22 H 34 O 2 79.95 40.57 found 80.22 40.28 In the manner indicated above, the following compounds from suitable reactants according to Example 26- cis-5-ε> (4,1-dimethylheptyl) -2-hydroxyphenyl; 7> 5-ethyl- cyclohexanone (4.54 g, 60%) from 5-ÅE-benzyloxy-4- (4,4-di- methylheptyl) phenyly-5-ethyl-2-cyclohexen-4-one (2.85 g, 6.55 mmol). Melting point 406-407 ° C. 4 IR: (CHCl 3) 5597, 5555, 4709, 4626 and 4585 cm -1.

Ms = (m / e) 544 (M0, 526, 515, 297, 275 and 259.

Analysis -% _Ü 5% H calculated for C 25 H 56 O 2 80.48 40.55 found 40.59 80.27 \ ¿'1 10 15 20 25 50 67 cis-5-yl (1,1-dimethylheptyl) -2-hydroxyphenyl7: 5¿ progazyclohexanone (1.66 g, 61%) from 5- [Albenzyloxy-4- (1,1- dimethylheptyl) phenyl715-propyl-2-cyclohexen-1-one (5.44 g, 7.62 mmol). Melting point 85.5-90, § ° C.

IR; (011015) 5555, 5289, 1700, 1610 and 157? oo “".

Ms = (m / e) 558 (rf), 540, 515, 297 and 275- Analysis -% C% H borel mode for 024155802 80.59 10.68 found 80.16 10.57 cis-5-(yl (1,1-dimethylheptyl) -2-hydroxyphenylyl-5-hexyl- cyclohexanone (5.06 U, 95%) from 5-Ealbenzyloxy-4- (1,1-di- methylheptyl) phenylyl5-hexyl-2-cyclohexen-1-one (4.00 g, 8.2 mmol). Melting point 84-85 ° C (after recrystallization from pentane).

IR; (0Hc15) 5571, 5555, 1705, 1625 and 1582 if '. ns: (m / e) 400 01+), 582 and 515.

Analysis -% C% H calculated for C 27 H 14 O 2 80.94 11.07 found 80.97 10.94 Example 50: transphosphorylbenzyloxy-4- (1,1-dimethylheptyl) -phenylZ; 5-methyl-cyclohexanone. To a solution of dimethyl copper lithium (2.47 mmol) in ether (5 mL) and hexane (2 mL), which solution had a temperature of 0 ° C, a solution was added dropwise of 5-Ealbenzyloxy-4- (1,1-dimethylheptyl) phenyl] 2- cyclohexen-1-one (500 mg, 1.24 mmol) in ether (1.5 mL).

The reaction mixture was stirred for 15 minutes and poured then in a saturated aqueous solution of ammonium chloride (500 ml). This interrupted the reaction and the reaction mixture was extracted with ether (5 x 50 ml). The combined ether the extracts were washed with water, then with a saturated sodium chloride solution, dried over magnesium sulfate and evaporated to give 475 mg (92%) of the title the compound in the form of an oil. ' na; (011015) 1704, 1615 and 1577 cm "". ms; (m / c) 420 (h, 402, 565, 555 and 529).

Exemgel §1: trans-5-α (1,1-dimethylheptyl) -2-hydroxyphenylyssal methyl cyclohexanone. A mixture of trans-5-β-benzyloxy- 4- (1,1-dimethylheptyl) phenyl] 15-methylcyclohexanone (175 mg, 10 15 20 25 50 55 68 0.417 mmol) and 175 mg of 5% palladium-on-carbon-50% water in methanol (8 ml) was stirred in hydrogen at a pressure of 1 atmosphere, until the hydrogen uptake subsided. Reaction mixture The filtrate was filtered through diatomaceous earth and the filtrate was evaporated. under reduced pressure. By crystallization of the pentane column obtained 89 mg (64%) of the title compound. with a melting point of 99-102 ° C. ~ Ms: m / e 550 (W), 512, 275 and 245.

Example 52:. nis-5 - [- 2-Benzylomi-4- (1,6-dimethylheptyl) purification trans- 5-methylcyclohexanol and the trans, cis isomer thereof. To one solution of trans-5-Albenzyloxy-4- (1,1-dimethylheptyl) phenyl] 5 # methylcyc10hexanone (500 mg, 10,714 mmol) in methanol (15 mL) tetrahydrofuran (5 ml), which solution had a temperature about -8 ° C, sodium borohydride (216 mg, 5.68 mmol) was added the course of 1 hour. The reaction mixture was further stirred 2 hours at -78 ° C, after which its temperature was allowed to rise room temperature. Then the reaction mixture was evaporated in vacuum and the residue was acidified with dilute hydrochloric acid. Where- after extraction was performed with ether and the extract was dried over magnesium sulphate, evaporated and the residue evaporated was purified by column chromatography on 50 g of silica gel.

Elution was performed with 50% ether-pentane to give first 252 may (77%) of the trans, cis isomer and then 45.9 mg (15%) of the cis, trans isomer. trans, cis: - Ms: (m / e) 422 (rf), 557, 514, 229 nnh 91.

Pm: δ 0.86 (n, terminal methyl), 1.05 (a, J = 7Hz, C-5 methyl), 1.26 (s, gem dimethyl), 5.70 (n, benzylic methine), 4.05 (n, carbinolmethine), 5.15 (s, benzylic methylene), 6.8- 7.0 (n, Ann) nnn'7,1-7, e (n, .AmH nen rn).

Eišiïåâåâ * _ 5 Ms; (m / e) 422 (rf), 557, 514, 229, 206 and 91.

Pm; 0.9 (n, terminal methyl), 1.05 (a, J = 7Hz, C-5 methyl), 5.1-4.5 (n, benzylic and carbinolmethines), 5.15 (s, benzyl iskethylene), 5.40 (s, OH) and 6.8-7.7 (n, Ph and ArH).

\ Z1 10 15 20 25 50 55 “<1 CO CD * SJ FD 69 Example §§: cis-5-Albenzyloxy-4- (1,1-dimethylhebtyl) phenyl7 cis- 5-methylcyclohexanol and the trans, trans isomer. To one solution of cis-5-ethylbenzyloxy-4- (4,4-methylethylneptyl) phenyl 5-Methylcyclohexanone (228 mg, 0.545 mmol) in methanol (10 mL) which solution had a temperature of -78 ° C, sodium borohydride (160 mg, 4.21 mmol) over 2 hours.

The temperature of the reaction mixture was then allowed to rise room temperature, whereupon the reaction mixture was added ether-saturated sodium chloride solution. The ether extract was dried over magnesium sulphate and evaporated under reduced pressure.

The evaporation residue was purified by preparative layer chromatography. double engraving on silica gel plates 20 x 20 x 0.05 cm, then elution was performed with 50% ether-pentane. One received 56 mg (16%) of the trans, trans isomer (Rf 0.25, silica) gel, 352% ether-petroleum ether) and 168 mg (Eph 0.17, silica dioxide gel, 55% ether (petroleum ether) of the cis, cis isomer.

Example 54: cis-5-ÅHW, 1-dimethylheptyl) -2-hydroxyphenylphecis-5 nervlnykionexnnnl. To a solution of cis-5-¿ÄL (4,4-ai- methylheptyl) -2-hydroxyphenyl 17β-methylcyclohexanol (896 mg, 2.15 mmol) in methanol (50 ml), which solution had a temperature At a temperature of -78 ° C, sodium borohydride (805 mg, 21.8 mmol) was added.

The reaction mixture was stirred for 1 hour at -78 ° C and its temperature was then allowed to rise to room temperature. Thereon the reaction mixture was added to ether and saturated sodium chloride solution. The ether extract was dried over magnesium sulfate and evaporated to give an oil. By re- crystallization in pentane obtained 589 mg (65%) of the title the compound having a melting point of 115-114 ° C.

IR: (cHCl) 5656, 5590, 4654 and 4592 cm -1.

Ms; (n / e) 552 (M *), 544, 247, 229 and 95.

Analysis -% C% H calculated for c22H56o2 - 79.46 40.94 found 79.79 10.62 The following compounds were prepared in the same manner suitable reactants: | .J \ (W IQ 10 15 25 STAY 55 í -.) '\ 70 (1,1-dimethylheptyl) -2-hydroxyphenyl γctzlczklchcxahcl (0.74 g, 74%) from cis-5-β1- (1,1- <11mchyl heptyl) -2-hydroxyphenyl7β-ethylcyclohexanone (1.00 g, 2.50 mmol). Melting point 110 ~ 111 ° C.

IR: (011015) 5656, 5567, 1651 and 1567 cm -1.

Analysis -% C% H calculated for C 25 H 58 O 2 79.71 11.05 found 79.41 10.71 cis-5-(LL (1,1-dimethylquypyl) -2-hydroxyphenyl; 7-cis-5- n-grggilcïhlchcxahcl (0.954 g, 71%) from cis-5-gI- (1n-di methylheptyl) -2-hydroxyphenyl7 ¥ 5-n-propylcyclohexanone (1.54 g, 5.74 mmol). Melting point 103-104 ° C (after recrystallization from pentane). (cucl> 5656, 5578, 1626 cch 1567 cm ”.

IR: ms; (m / c) 560 (MÜ, 542, 275, 257 and 161.

Analysis ~% C% H calculated for 024114002 79.94 11.18 i found 79.88 11.22 cis-5-1α (1,1-dimethylheptyl-2-hydroxyphenyl) -acis-5- n-hegglcycldhexanol after purification on 120 g of silica gel and elution with 50% ether-pentane. Quantitative yield in the form of an oil containing a trace amount of trans, the trans isomer, cis-5-α (1,1-dimethylheptyl) -2-hydroxyphenyl [5] hexane (1.2O g, 5.00 mmol). 1 (0Hc1) 5625, 5555, 1626 and 1565 cm (fc / c) 402 (rf), 564, 517 cch 299.

Example ââz trans-β (1,1-dimethylheptyl) -2-hydroxyphenyl] cis 5-methylcyclohexanol. A mixture of trans-5-β-benzyloxy-4- (1,1-dimethylheptyl) phenyl] lcis-5-methylcyclohexanol (220 mg, 0,521 hmcl) cch 220 mg 5% pa11aaiumfpà-kc1-50% xícthch i methanol (8 ml) was stirred under hydrogen at a pressure of 1 atmosphere for 5 hours. The reaction mixture was filtered through slides. tomato soil and the filtrate was evaporated. By crystallization of the evaporation residue in petroleum ether, 91 mg was obtained (55%) of the title compound. Melting point 111-112 ° C.

IR; (cHc1) 5571, 5555, 1629 and 1572 cm -1.

Ms; (m / c) 552 (rf), 514, 246 and 229.

In the same manner the following compounds were prepared from IR: MS: suitable reactants: \ I1 10 45 20 25 50 55 40 . 7SÛ9ÛJÜ'2 71 cis-5-β (1,1-dimethylheptyl) -2-hydroxypheno2? 5-Methyloicyclohexanol (20.0 mg, 56%) as an oil Cis-5-ε Ebenzyloxy-4- (1,1-dimethylheptyl) phenyl7-trans-5- methylcyclohexanol (45 mg, 0.107 mmol) as an oil.

High resolution Ms: (m / e) 552, .269a (Mi 022515602), 51u, 2655; 247.1657 and 229.16oo. trans; 5f111 (1,1-dimethylheptyl) -2-hydroxyphenyl7 5-Methicyclohexanol (28 mg, quantitative yield) from the trans- 5+ 2-Benzyloxy-4- (1,1-dimethylheptyl) phenyl] trans-5-methyl- cyclohexanol (56 mg, 0.0855 mmol). The product was obtained in mold of an oil.

Ef = 0.55 (silica gel, 50% ether-pentane). cis-5-ε> (1,1-dimethylheptyl) -2-nyaroxyphenyg7ècis-5- Methylcyclohexanol in quantitative yield from cis-5- [É ¥ benzyloxy ~ 4- (1,1-dimethylheptyl) phenylylcis-5-methylcyclohexanol (168 mg, 0.598 mmol). This compound was identical to the product of Example 54.

Example 6: trans15-β (1,1-dimethylheptyl) -2-hydroxyphenyl? elcis-4- (2-propenyl) cyclohexanol. A solution of trans-5-β-benzyloxy- 4- (1,1-dimethylheptyl) phenyl] cis-4- (2-propenyl) cyclohexanol (900 mg, 2.01 mmol) and 2.74 ml of 2,2-molar n-butyllithium (i hexane) in ether (5 ml) was stirred for 2 days at room temperature.

A second 2.0 mmol portion of n-butyllithium was added and the reaction mixture was stirred for an additional 2 days. Reactional the mixture was added to a saturated ammonium chloride solution (250 ml) and the mixture was extracted with ether: the ether extract was dried over magnesium sulphate and evaporated. The evaporation residue was purified by column chromatography on 20 g of silica gel and elution was performed with 50% ether-pentane, thereby obtained 651 mg (88%) of the title compound, m.p. 85 ~ 91 ° C. .

IR; (cnci) 5511, 1659, 1616 och 1567 om ”.

Ms = (m / e) 558 (MH +, 545, 540, 516, 299, 275 and 255).

In this way: cis-5- [α (1,1-dimethylheptyl) -2-hydroxyphenyl] α trans-4- (2-propenyl) cyclohexanol (241 mg, 60%) from cis-5- 4- (1,1-Dimethylheptyl) phenyl] trans-4- (2-propenyl) -cyclohexanol (500 mg, 1.12 mmol). Melting point 124-125 ° C (after recrystallization in pentane). 7809060-2 10 45 20 25 5 50 35 40 72 m; (cnclš) 5571, 5555, 1642, 1618 and 1580.

Ms; (m / e) 558 (MW, 540, 298, ass, 275 and 255.

Analysis -% c% H calculated for 024H5802 80.59 40.68 found 80.52 40.57 Example 52: trans-5-α (4,4-dimethylheptyl) -2-hydroxyphenyl (2-propenyl) cyclohexanone. To a solution of 5-¿ÃÄ (4,4-di- methylheptyl) -2-hydroxyphenyl] -4- (2-propenyl) cyclohexanol (2.45 g, 6.05 mmol) (mixture of isomers) in dichloromethane (45 mL) was added pyridinium chlorochromate (2.59 g, 42.4 mmol).

The reaction mixture was stirred for 2 hours at room temperature. diluted with ether, diatomaceous earth was added and the mixture was filtered through magnesium sulfate. The filtrate was evaporated and was purified by column chromatography on 200 g of silica dioxide gel. Elution was performed with 20% ether pentane and man received 250 mg of the crude title compound. This was purified further by preparative layer chromatography on two silica gel plates 20 x 20 x 0.2 cm and elution through-0 was run twice with 20% ether-pentane to give 200 må (9.5%) of the title compound in the form of an oil. ' IR: (CHCl 3) 5574, 5590, 4718, 4650, 4626 and 4577 Qmëq.

Ms = (m / e) 556 (f), w, 558, 544, 2e8, .2v1, 257, 255 and 229. _ .i 5 % HRS Analysis -% C calculated for C24H5602 80.85 40.48 found 80.92 9.86- Example 8: - : rans-æß-benzyloxy-u- (fl, 1- <1imew1nepgy1) fsny; 7; 5 _-_ (2-propenyl) -cyclohexanone-ethylene ketal. A mixture of trans-5-Albenzyloxy-4- (4,4-dimethylheptyl) phenyl] -4- (2- propenyl) cyclohexanone (47.0 g, 58.4 mmol), ethylene glycol (47.2 g, 0.762 mol) and p-toluenesulfonic acid monohydrate (250 mg) in benzene (200 ml) was heated at reflux temperature in 5 hours with a Dean-Stark trap. The reaction mixture was cooled and was added to a mixture of 4N> NaOH (200 mL), ether (400 mL) _ ml) and pentane (400 ml). The organic extract was washed with water (2 x 200 ml), with a saturated sodium chloride solution (2 x 200 ml), dried over magnesium sulphate and evaporated, whereby the title compound was obtained in quantitative yield.

\ J'l 10 45 fu V1 55 7809060-2 e 73 IR; (CHCl 3) 4656, 4626 and 4567 6m

MS: (m / e) 490 (M &lt; + &gt;), 475, 450, 449, 448, 446, 407, 405, 599, 583 and 94- Example 52: trans-5-Albenzyloxy-4- (4,1-dimethylheptyl) -phenyl7S4; (2-butenyl) cyclohexanone. A mixture of trans-5-β-benzyloxy- 4- (1,6-Dimethylheptyl) phenyl] -4- (2-butenyl) cyclohexanone-ethylene- ketal (700 mg, 4.58 mmol), dioxane (20 mL) and 2NHCl (20 mL) was heated at reflux temperature for 4.5 hours. Reactive The ionic mixture was cooled, poured into ice water (500 ml) and was extracted with ether (500 ml). The ether extract was washed with a saturated solution of sodium bicarbonate (200 ml), dried over magnesium sulphate and evaporated to give the title compound in the form of an oil and quantitative yield.

IR; (CHG15) 4745, 4646 and 4575 6m ''.

Ms = (m / e) 466 (M0, 405, 575, 569, 565, 545, 275, 274 and 91.

Rf: 0.45 (silica gel, 25% ether-pentane).

In the same way it was prepared: Trans-5-benzyloxy-4- (1,1-dimethylheptyl) phenyl] §4 (2-nentenyl) cyclohexanone in quantitative heat in the form of a trans-5- [2-benzyloxy-4- (1,1-dimethylheptyl) -phenyl] oil 4- (2-pentenyl) cyclohexanone-ethylene ketal (540 mg, 40.04 mmol).

Rf: Ememgel 40: cis-5-[(4,1-dimethylheptyl) -2-hydroxyphenyl] cis-4 methyl cyclohexanol and cis-5- 4- (1,1-dimethylheptyl) -2- hydroxyphenyl7 ¥ 4 ~ methylcyclohexanone. A mixture of 5-ÅÉÄ benzyloxy-4- (1,4-dimethylheptyl) phenyl-4-methylcyclohex-2- enone and 591 mg of 5% Pd-on-carbon-50% water in methanol (15 ml) was stirred in hydrogen at a pressure of 1 atmosphere, until hydrogen uptake declined. The reaction mixture was filtered through diatomaceous earth with ethyl acetate and evaporated. The remainder was purified by column chromatography on silica gel and elution was performed with (200 g) 50% ether-hexane, varying by first obtaining 758 mg of a mixture of ketones and then 820 mg (55%) of the title alcohol, which crystallizes des and cyclohexane. The mixture of ketones was further purified by preparative layer chromatography on five silica gel 0.57 (silica gel, 53% ether pentane). 10 45 20 25 50 55 40 74 plates 20-x 20 x 0.2 cm and elution was performed four times with dichloromethane to give 412 mg (7.2%) of the rubric tone in the form of an oil. i Rubrikalkcnclcn: Melting point 154-155 ° C.

IR; (cacl) 5625, 5555, 1626cc11 1585 ccfl.

Ms; (m / c) 552 (W), 514, 247 and 229. c Analysis -% C% H calculated for cæašeoa 79.46 10.92 found 79.40 10.72 Headline tone: IR; (oaciš) 5625, 5590, 1654 and 1582 cm ”.

Ms: (m / c) 55 (W), 515, 512, 286, 275, 271 and 245.

Exemgel 4¶: 7 5- (2-Benzyloxy-4- (1,4-dimethylheptyl) phenyl) -5-methoxy- 6-methyl-2-cyclohexen-4-one. To a solution of 0.5 mol of lithium iodoisopropylamide in 500 ml of tetrahydrofuran (50.5 g, 0.5) moles of diisopropylamine and 447 ml of 1,2-molar-n-butyllithium i hexane), which solution had a temperature of -78 ° C, was added dropwise (50 ml) of a solution of 217 g (0.5 mol) of 5- (2- benzyloxy-4- (4,1-dimethylheptyl) phenyl) -5-methoxy-2-cyclohexene- 4-one in 250 ml of tetrahydrofuran. The reactive mixture was stirred for a further 50 minutes at -78 ° C, then 479 g were added (1.0 mol) of hexamethylphosphoramide and 78.4 g (0.55 mol) of methyl iodide. The temperature of the reaction mixture was allowed to rise slowly to room temperature, stirred for 1 hour and the reaction was broken by adding 10 ml of water. The reaction mixture evaporated under reduced pressure to remove the tetrahedron. the hydrofuran and 1 liter of ice water-1 liter of ether was added. Ether- the extract was washed with water (5 x 1 L), dried over magnesium sulphate and evaporated to give the title the association in almost pure form. The title association was purified with by column chromatography on 2 kg of silica gel and eluted with ether-pentane. IN Example 42: 5- [α-benzyloxy-4- (1,1-dimethylheptyl) phenyl] -5,4-dimethyl- 2-ozlohexen-1-one. In the manner set forth in Example 1 were reacted 5-β2-Bicyclicyl-4- (1,1-dimethylcycyl) phenyl-cycloxy-e-methyl 2-cyclohexen-1-one by Grignard reaction with methylmagnesium- iodide to the title compound. 5 lO 45 20 25 50 55 one co ca wo ca cm -13 | 75 By debenzylation of the product in the manner specified in Example 2 the corresponding phenol was obtained.

Example 4§: 271'-hydroxy-4- (1,1-dimethylheptyl) phenyl] 4,5-dimethyl- clklohexanol. The benzylated compound of Example 42 was reduced with sodium borohydride in the manner set forth in Example pile 11 to the headline association. ämleelillr Phenybenzyloxy-4- (1,1-dimethylheptyl) phenyl] 4,5-di- methylcycloheptanone. To a solution of 17.4 g (0.01 mol) dibromomethane and 24.7 g (0.050 mol) of 3-1'-benzyloxy-4 - (¶, 1- dimethylheptyl) phenyl7,5,4-dimethylcyclohexanone in 100 ml of tetra- hydrofuran, which solution had a temperature of -78 ° C, a solution of lithium solution was added dropwise over 2 hours. dicyclohewlamide (uno moi) in 100 ml of tetrahydrofuran. Reactive The ion mixture was stirred for an additional 4 hours at -78 ° C and the reaction was quenched by the addition of 2 ml (0.44 mol) water. The reaction mixture was added to 500 ml of ether and 200 ml of water. The ether extract was dried over magnesium sulfate and evaporated. The crude product was purified by column chromatography on 500 g of silica gel and elution through was carried out with ether-pentane to give pure 5-1 oxy-4- (1,1-dimethylheptyl) phenyl] -4-dibromomethyl-4,5-dimethyl- cyclohexanol.

To a solution of 50.4 g (0.05O mol) of 5-ethylbenzyloxy- 4- (4,4-dimethylheptyl) phenyl] -1H-dibromomethyl-4,5-dimethylcyclo- hexanol in 150 ml of tetrahydrofuran, which solution had a temperature of -78 ° C, was set slowly over 2 hours 47.7 ml (0.105 mol) of n-butyllithium (2.2 M in hexane). Reactional the solution was stirred for an additional 2 hours at -78 ° C and 10 minutes at 0 ° C, after which the reaction was stopped by the mixture was poured into 500 ml of ice-cold 1N> HCl. It was then extracted the reaction mixture with ether (2 x 250 ml), they combined the extracts were washed with 250 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated. Evaporation the residue was purified by column chromatography on 500 g silica gel and elution were performed with ether-pentane, whereby the title compound was obtained.

IJ CO (TJ \ Qg f.) u 10 15 20 25 50 55 Û WD 76 Example 42: General hydrochloride formation. H01 was led in surplus into a solution of the appropriate compound of formula IA-ID containing holding a pyridyl group and the precipitate formed was separated and recrystallized from a suitable solvent, for example methanol-ether (1:10). 5 In an analogous manner hydrobromide, sulphate, nitrate, phosphate, acetate, butyrate, citrate, malonate, maleate, fumarate, malate, glycolate, gluconate, lactate, salicylate, sulfosalicylate, succinate, pamoate, tartrate and embonate. IN Example 46: t cis-5- [α- (1,1-dimethylheptyl) -2-hydroxyphenyl] cyclo- hexanol-2'-O-hemisuccinic acid ester sodium salt. To a solution of 4.00 g- (5514 mol) cis-s-ß- (f: 1,1-dimethylheptyl) -2-hydroxy- phenyl7cyclohexanol in 5 ml of dichloromethane, which solution had a temperature of 0 ° C, 0.585 g (5.14 mmol) of 4-N, N-dimethyl- aminopyridine. To the solution thus obtained was added slowly 0.514 g (5.14 mmol) of succinic anhydride in 1 ml of dichloromethane.

The reaction mixture was stirred for 4 hours at 0 ° C, then 5.14 ml of 1N-HCl was slowly added. The reaction mixture was stirred for a further 5 minutes and then added to 100 ml of water 100 ml of dichloromethane. The dichloromethane extract was dried over magnesium 'sulfate and evaporated. The evaporation residue was dissolved in 5 ml of ethanol and 5.14 ml of a 1-normal solution of NaOH in ethanol was added. The ether addition caused the crystalline isation. Recrystallization from ethanol-ether gave the title Association.

Example 47: cis5- [N- (1,1-dimethylheptyl) -2-hydroxyphenyl] -cyclo- hexanol-O'-O-phosphoric acid ester monosodium salt. To an up- slurrying of 0.126 g (5.14 mmol) of potassium hydride in 5 ml of dimethyl formamide, which slurry had a temperature of 0 ° C, was added a solution of 1.00 g (5.14 mmol) of cis-5- [N- (1,1-dimethylheptyl) - 2-hydroxyphenyl7cyclohexanol in 5 ml of dimethylformamide. Sedan gas- the development subsided (after about 10 minutes) was added slowly 0.952 g (5.14 mmol) of dibenzylphosphorochloridate and the reaction mixture was stirred for 1 hour, then added to 200 ml of ether-100 ml of water. The ether extract was washed with 10 15 20 25 50 * J CD CD \O CD Gx "oh IN FO 77 water (2 x 100 ml), dried over magnesium sulphate and fumes. The evaporation residue was mixed with 1.0 g of 5% platinum-on-carbon and 25 ml of ethanol and stirred in hydrogen with a pressure of 1 atmosphere for 5 hours. The reaction mixture is filtered. through diatomaceous earth and 5.14 ml of a 1-normal solution of sodium hydroxide in ethanol was slowly added to the filtrate.

Upon addition of ether, the product crystallized out and the crystallized in ethanol to give the title compound. units.

Example 48: 5-Acet (1,1-dimethylheptyl) -2-hydroxyphenygybyclohexanol (100 mg) was intimately mixed and ground with 900 ml of starch.

The mixture was charged into collapsible gelatin capsules, so that each capsule contained 10 mg of the compound and 90 mg of starch.

Example G9: A tablet base was prepared by mixing the following ingredients: Sucrose 80.5 parts Tapioca starch 15.2 parts Magnesium stearate 6.5 parts A sufficient amount of trans-5- [Hydroxy-4- (2- (5-phenyl- Phentyloxy) phenyl7byclohexanol was mixed into this base and tablets containing 0.1 were prepared therefrom; 0.5; 1; 5; 10 and 25 mg of the compound.

Example 50: Suspensions of 5-α (1,1-dimethylheptyl) -2-hydroxy- phenylfoyclohexanone was prepared by adding 0.5% methylcellulose provided sufficient amounts of the compound obtaining suspensions containing 0.05; 0.1; 0.5; 1; 5 and 10 mg of the compound per ml. 10 15 20 25 50 55 78 Preparation of the starting materials is illustrated in the following Example A - Z.- Example A: 2- (5-benzyloxyphenyl) -2-methylpropionitrile. To one solution of 1500 ml of dimethyl sulfoxide saturated with methyl bromide a solution of 295 g (1.52 mol) of 2- (5-benzyl) oxyphenyl) acetonitrile in 200 ml of dimethyl sulfoxide and 420 ml of a 50% aqueous solution of sodium hydroxide. Methyl bromide bubb- was continuously introduced through the reaction mixture during said addition. batches (50 minutes) and then for another 1.5 hours while maintaining the temperature of the reaction mixture at 50 ° C cooling with ice. The reaction mixture was added to 2 l of water. 2 kg of ice and the mixture thus obtained was extracted with ether (4 x 1 1). The combined ether extracts were washed with water (2 X 1 1) and then once with 1 l of a saturated sodium chloride solution, dried over magnesium sulfate and evaporated, whereby 525 g (98%) of the product were obtained in the form of an oil. m; (c fl cl) 2247, 1616 och 1605 om ”.

Ms: m / e 251 (rf), 256, 160 and 91.

Example B: 2- (5-benzyloxyphenyl) -2-methylpropionaldehyde. To one solution of 525 g (1.25 mol) of 2- (5-benzyloxyphenide) -2-methyl- propionitrile in 1.85 l of tetrahydrofuran, which solution had a temperature of 15 ° C, 1.6 moles of diisobutylaluminum hydride in the form of a 1.5 molar solution in hexane (reaction the temperature was kept at 15-18 ° C). Temperature of the reaction mixture temperature was allowed to rise to room temperature and the the mixture was stirred for a further 2 hours. It was then interrupted the reaction by adding a solution of 170 ml of concentrated sulfuric acid in 670 ml of water (temperature fi50 ° C). It is so- the temperature of the mixture was allowed to rise to room temperature. and then stirred for a further 2 hours. The the organic phase was separated and the aqueous phase was extracted. cured once with 1 L of ether. The combined organic phases was washed with 500 ml of water and 500 ml of a saturated sodium chloride solution, dried over magnesium sulphate and evaporated, whereby 515 g (99%) of the title compound were obtained. m; (estimate) 1742 and 1615 if ”.

Ms: 254 (W), 259 and 91. 10 15 20 25 50 55 40 \ a ca F: wa ca cm -3 | ma 79 Example C: 1-Benzyloxy-5- (1,1-dimethyl-2-heptenyl) benzene. To one_ solution of 1.8 moles of dimsyl sodium (made from sodium hydride) and dimethyl sulfoxide) in 2 L of dimethyl sulfoxide, which solution had a temperature of 15 ° C, 768 g (1.8 mol) were added portionwise pentyltriphenylphosphonium bromide. The slurry thus obtained was stirred for 15 minutes at 15-20 ° C and then added 5.5 g (1.24 mol) of 2- (phybenzyloxyphenyl) -2-methylpropionaldehyde (reaction temperature S50 ° C). The mixture thus obtained was stirred for 4 hours at room temperature and then added to 6 l of ice water, whereby the reaction was stopped. Extraction was performed with 50% ether-pentane (4 x 1 L). They combined the extracts were washed with water (2 x 1 l) and once with 1 l washed sodium chloride solution, dried over magnesium sulfate and evaporated to give an oil. Through crystalline lization of this oil in 50% ether-pentane (for removal triphenylphosphine oxide), filtration and evaporation of 559 g of oil were obtained. The crude oil was purified by column chromatography on 2 kg of silica gel and elution through was carried out with 20% hexane-dichloromethane to give 217 å (57%) of the product in the form of an oil.

Ifa; (cHc1) 1610 and 1587 if '.

MS: m / e 508 (M &lt; + &gt;), 295, 274, 265, 251, 259, 225, 21? and 91. ' In a similar manner, 1-benzyloxy- (1,1-dimethyl- oct-2-enzylbenzene (15.5 g, 70%) from 15.75 (0.062 mL) 2- (5-Benzyloxyphenyl) -2-methyl-propionaldehyde and 57.5 g (0.0899 mol) hexyltriphenylphosphonium bromide. The product was an oil.

IR; (cnci) 1608 and 1582 on ".

Ms: m / e 522 (rf), 507, 279, 274, 285 and 251. Benzyloxy-5- (1,1-dimethyl-2-propenyl) -benzene in the form of an oil (25.0 g, 91%) from 2- (5-benzyloxyphenyl) -2-methyl- propionaldehyde (25.5 g, 0.10 mol) and methyltriphenylphosphonium bromide (40.5 g, 0.115 mol).

IR; (cnciš) 1,850, 1608 and 1587 cm ”.

Ms; m / e 252 (rf), 257, 185, 181 and 91. 1-benzyloxy-5- (1,1-dimethyl-2-butenyl) benzene in the form of an oil (57.5 5.77%) from 2- (5-benzyloxyphenyl) -2 + methyl- propionaldehyde (46.2 g, 0.182 mol) and ethyltriphenylphosphonium bromide (75.0 g, 0.202 mol). 10 15 20 25 50 55 60 ~ 1R = (0261) 4664, 4626, 4624, 4606 and 4567 6m '“. ms; m / 6 266 (M +), 254, 226, 465, 475 and 94. 4-Benzyloxy-5- (1,1-dimethyl-2-pentenyl) benzene in form of an oil (54 g, 74%) from 2- (5-benzyloxyphenyl) -2-methyl- propionaldehyde (40.0 g, 0.157 mol) and propyltriphenyl- phosphonium bromide (66.7 g, 0.175 mol).

IR: (CHCl 3) 4626 and 4600 6mf Ms: (m / 6) 260 (mf), 265, 254, 257, 225, 244, 469, 147 and 91. 1-Benzyloxy-5- (1,4-dimethyl-2-hexenyl) benzene in form of an oil (55 g, 76%) from 2- (5-benzyloxyphenyl) -2-methyl- propionaldehyde (40.0 g, 0.457 mol) and butyltriphenylphosphonium bromia (69, o g, o, 475 m61 \. 'i IR; (cHo15) 4625 and 46oo 654 ' ns: (m / 6) 294 (M +), 279, 265, 254, 255 and 94. 4-Benzyloxy-5- (1,1-dimethyl-2-nonenyl) benzene in form of an oil (54.5 g, 75%) from 2- (5-benzyloxyphenyl) -2-methyl- propionaldehyde (40.0 g, 0.457 mol) and heptyltriphenylphosphonium bromide (60.0 5, 0.158 mol). ' 2Rf: 0.72 (silica gel, 55% ether-cyclohexane). 1-Benzyloxy-5- (1,1-dimethyl-2-decenyl) benzene in form of an oil (45 g, 78%) from 2- (5-benzyloxyphenyl) -2-methyl- propionaldehyde (40.0 g, 0.457 mol) and octyltriphenylphosphonium bromide (84.0 g, 0.478 mol).

IR; (cHc1) 4624 and 46oo 6mï “. ms; (m / 6) 55o (M +), 555, 506, 264, 265, 254 and 94. 4-Benzyloxy-5- (4,1-dimethyl-2-undecyl) benzene in the form of an oil (56 g, 65%) from 2- (2-benzyloxyphenyl) -2-methylpropion- aldehyde (40.0 g, 0.157 mol) and nonyltriphenylphosphonium bromide (64.4 g, 0.475 mol). in : R = (cHc1) 4645 and 4592 @mf '.

Ms; (m / 6) 564 (M +), 549, 524, 295, 275, 254 and 94.

Example D: 5- (4,1-Dimethylheptyl) phenol. A mixture of 65 g (0.24 fl mol) 2- (5-benzyloxyphenyl) -2-methyl-cis-oct-5-ene and 7.5 g, 40% palladium-on-carbon in 100 ml of ethanol was hydrogenated in 4 hours in an apparatus according to Parr at hydrogen pressure of 545 kPa.

Additional servings of 7.5 E 10% palladium-on-carbon each was added after the reaction lasted for 1 and 2 hours, respectively 10 15 20 25 50 55 40 81 and the reaction was continued for another 12 hours. Reactional the mixture was filtered through diatomaceous earth with ethanol and the filtrate was evaporated to an oil. The oil was purified through column chromatography on 1 kg of silica gel and elution was carried out with 50% hexane-dichloromethane to give 105 g (78%) of the product as an oil.

IR; (cH01¿) 5571, 5511 ooh 1592 om '“.

M8; m / o 220 (M *), 205 ooh 155.

In the same manner, 3- (1,1-dimethyloctyl) phenol was prepared In an orhyoo of 82% (7.8 g) or 15.0 g (0.0406 mol) of 1-honsyl oxy-5- (1,1-dimethyl-oct-2-enyl) benzene. It was obtained in the form of an oil having the following characteristics IR: (CHCl 3) 5571, 5279, 1565 and 1527-1. ms; m / o 254 (h *), 219, 191, 178, 164, 149, 155 ooh 121. 5-§1,1-dimethyl1lQr0Q1l2phenol in the form of an oil (11.7 g, 78%) from 1-benzyloxy-5- (1,1-dimethyl-2-propenyl) benzene (25.0 g, 0.0912 mol). 1R = (0Hc1) 5554, 5500, 1615 ooh 1587 om "“.

Ms; m / o 164 (M *), 149, 155 ooh 108. 5- (1,1-dimethylbutyl) phenol in the form of an oil (21.0 g, 84%) from 1-benzyloxy-5- (1,1-dimethyl-2-butenyl) benzene (57.5 g, _ 0.140 mol). rn; (0Hc15) 5625, 5448 ooh 1615 om "“.

M8: m / o 178 (M *), 165, 155, 121 ooh 107. 5- (1,1-dimethylpentyl) phenol in the form of an oil (16 g, 75%) of 1-benzyloxy-5- (1,1-dimethyl-2-pentenyl) benzene (51.0 g, 0.111 mol). « IR: (CHG15) 5656, 5590, 1654, 1625 ooh 1605 om * “. us: (m / o) 192 (M *), 155 ooh 108. 5- (1,1-dimethylhexyl) phenol in the form of an oil (18 g, 74%) of 1-benzyloxy-5- (1,1-dimethyl-2-hexenyl) benzene (55.0 g, 0.119 mol).

IR = (OHH15) 5650, 5590 ooh 1626 (fraction) om'7. ms; (m / 6) 206 (M *), 191, 177, 165, 149 ooh 155. 5- (1,1-dimethylonymyl) phenO1 in the form of an oil (20.6 g, 86%) of 1-benzyloxy-5- (1,1-dimethyl-2-nonenyl) benzene (54.5 g, 0.105 mol). '' IR; (0Hc15) 5656, 5578 ooh 1615 (crime) om '“.

M6; (m / o) 248 (M *), 255, 192, 178 ooh 155. 7809060-2 O 10 15 20 25 50 35 82 i I; 1 5-§1,1-dimethyldecylphenol in the form of an oil (21.0 g, 65%) from 1-benzyloxy-5- (1,1-dimethyl-2-decenyl) benzene (45.0 g, 0.125 mol).

IR: (CHCl 3) 5656, 5555 and 1615 (thirty} cm -1.

FIS: - 262 (IVF), 24-7, 206, 191, 178, 466, 155 and 155. 5- (1,1-dimethylundecyl) phenol in the form of an oil (21 g, 77%) of 1-benzyloxy-5- (1,1-dimethyl-2-undecenyl) benzene (58 o, 0.099 mel). '" m; (chcl D 5554, 5279 ooh 159? om "".

Ms; (m / o) 278 (rf), 281, 220, 184 ooh 155.

Example E: 2- (4-bromo-5-hydroxyphenyl) -2-methyloctane. To a solution of 110 g (0.50 mol) of 2- (5-hydroxyphenyl) -2-methyloctane in 200 ml carbon tetrachloride, which solution had a temperature of 0 ° C, a solution of 80 g (0.50 flour) of bromine in 90 ml was added dropwise carbon tetrachloride (reaction temperature fi50 ° C while cooling).

The reaction mixture was stirred for an additional 15 minutes and then evaporated to dryness to give 150 g (100%) product in the form of oil. m; (011015) 5559, 5289 ooh 1585 oil.

Ms; (111/83500, 289 (M *), 215, 215, 201, 199, _187 ooh 185.

In a similar manner, 2- (4-bromoph5-hydroxyphenyl) - 2-methylnonane in a yield of 82% (8.5 g) as an oil from 7.8 g (0.055 mol) of 2- (5-hydroxyphenyl) -2-methylnonane: m; (011015) 5279, 1815 ooh 1587 om ”.

Ms; (m / o) 514, 512 (M *), 212, 210, 185 ooh. 187. 2- (4-bromo-5-hydroxyphenyl) -2-methylbutane in the form of a oil (12.7 g, 98%) from 2- (5-hydroxyphoyl) -2-motylhutone (950 g, 0.057? 11101).

IR; (021015) 5521, 5279, 1808, 1800 ooh 1577 om ”.

Ms; (m / omau, 242 (M *), 229, 227, 215, 215, 187 ooh 185. 2- (4-bromo-5-hydroxyphenyl) -2-methylpentane in the form of a oil (29.9 g, 99%) from 2- (5-hydroxyphenyl): 2-methylpentane (21.0 g, 0.118 mol). g IR; (011015) 5810, 5555, 1818 ooh 1800 om fl.

Ms; (m / o J 258, 258 (M +), 245, 241, 215, 215, 201, 199, 187 and 185. 40 45 20 25 50 7809Û6G ~ 2 55. 2- (4-bromo-5-hydroxyphenyl) -2-methylhexane as a oil (22.8 g, 100%) from 2- (5-hydroxyphyl) -2-methylhexane (16.0 g, 0.0855 mol).

IR: (CHCl 3) 5610, 5555 and 1600 cm -1.

Ms = '(m / c) 272 and 270 (M *), 215, 215, 187 (S, gum dimethyl), (5, §5 (broad, OH), 6.84 (then, J = 8 and 2HZ, ÄIH), 7.09 (d, J = 2Hz, AIK) and 7.42 (d, J = 8Hz, ArH). 2- (4-bromo-5-hydroxyphenyl) -2-methylheptane as a oil (quantitative yield) from 2- (5-hydroxyphenyl) -2-methyl- hcphah (20.0 g, 0.971 mol).

IR = (chclš) 5584, 5555 and 1600 om '“.

MB: (m / e) 286 And 284 (N +), 215, 245, 487 And 185. 2- (4-bromo-5-hydroxyphenyl) -2-methyldecane in the form of a oil (25.2 g, 85%) from 2- (5-hydroxyphenyl) -2-methyldecane (20.6 g, 0.051 mol).

IR; (chclš) 5571, 5555 and 1661 if "".

MS: (Q / e) 528 Och 526 (M +), š fi š, 344, 215 Och 215. 2- (4-bromo-5-hydroxyphenyl) -2-methylundecane in the form of a oil (quantitative yield) from 2- (5-hydroxyphenyl) -2-methyl- can (21.0 g, 0.0802 mol).

IR: (CHCl 3) 5571, 5555 and 1600 (fraction) ch +.

Ms: (h / o) 542 and 540 2- (4-bromo-5-hydroxyphenyl) -2-nityldodecane in the form of a oil (22.0 g, 84%) from 2- (5-hydroxyphenyl) -2-methyldodecane (21.0 g, 0.0764 mol).

IR: (OHClS) 5597, 5555, 1615 and 1592 cm -1.

Ms; (m / c) 556 and 554 (M *), 540, 558, 215 and 215.

Example F: 2- (5-Benzyloxy-4-bromophenyl) -2-methyloctane. To one slurry of 25.0 g (0.575 mol) of potassium hydride in 400 ml N, N-dimethylformamide, which slurry had a temperature of -18 ° C, a solution of was added over 45 minutes 450 g (0.5 mol) of 2- (4-bromo-3-hydroxyphenyl) -2-methyloctane i 400 ml N, N-dimethylformamide (reaction temperature few -15 ° C).

The reaction mixture was stirred for an additional 45 minutes. then a solution of 98.5 g (0.575 mol) of benzyl bromide in 200 ml N, N> dimethylformamide was added. The mixture was heated to room temperature and stirred for an additional 50 minutes.

The reaction was quenched by the addition of 6 L of ice water, whereupon 7 8 10 15 20 50 55 G EPC -2. 84 6 extraction was performed with ether (6 x 500 ml). They combined the extracts were washed with water (2 x 1 L) and with a saturated sodium chloride solution (1 x 1 L), dried over magnesium sulfate and evaporated. Quantitative yields were obtained the headline association., ' m: (08013) 4592 and 4575 om ”.

N01 (m / eÜ5901 588 (M +) 1 5751 5751 5541 552, 5051 505 and 91.. 2- (5-Benzyloxy-4-bromophenyl) -2-methyl-nonane was prepared in a yield of 95% (10.4 g) of 2- (5-hydroxy-4-bromophenyl) - 2-111coy111onc1n (8.5 g, 0.027 mcl), nictriomhydride (05744 g, 0.051 mol) and benzyl bromide (5.5 g, 0.051 mol) in the form of a oil. m; (01101) -4800 and 4575 c111 "". c me; (111 / cy104, 402 (W), 505, 505, 94. 2- (5-Benzyloxy-4-bromophenyl) -2-methylpropane (46.5 g, 88%) from 2- (4-bromo-5-hydroxyphenyl) -2-methylpropane (58.0 g, 0.166 mol).

Melting point 52-54 ° C (after recrystallization from pentane). m: (OHH1) 4800 and 4585 c111 "'.

Ms; (111 / o) 520, 548 (rf), 505, 505, 259 and 225. 2- (5-Benzyloxy-4-bromophenyl) -2-methylbutane in the form of a oil (24.9 S, 99%) from 2- (4-bromo-5-hydroxyphenyl) -2-methylbutane _ (1715 81 010777 11101) - 1111 (011015) 4800 and 4585 cufq.

N52 (m / e) 554, 552 (M +), 5191 517, 5091 5051 2551 225 and 91. 2- (5-Benzyloxy-4-bromophenyl) -2-methylpentane in the form of a oil (5415 81 99%) from 2- (4-bromo-5-hydroxyphenyl) -2-methylpentane (25, g, 0.100 mol). * m: (011015) 4640 and 4595 c111 "'.

Ms: 1111/0598, 546 (M0, 555, 554, 505, 505 and 94. 2- (5-Benzyloxy-4-bromophenyl) -2-methylhexane in the form of a oil (50 g, 98%) from 2- (4-bromoph5-hydroxyphenyl) -2-methylhexane (22.7 g, 0.0854 111o1). a In; (Choi) 4805 and 4592 c111 "".

N81 (111/13 585 and 564 (W), 505 and 505. 2- (5-Benzyloxy-4-bromophenyl) -2-methylheptane in the form of a oil (quantitative yield) from 2 ~ (4-bromo-5-hydroxyphenyl) ~ 2- Methylheptane (25.0 g, 0.0806 mol). 10 15 20 25 50 7 8090 1 85 IR; (chc15) 16oo cch 1582 cm ”.

Ms = (m / e) 576 and 574 (rf), 505, 505, 215 and 215 2- (5-Benzyloxy-4- (bromophenyl) -2-methyldecane in the form of an oil (quantitative yield) from 2- (4-bromo-5-hydroxyphenyl) 2-Methyldecane (25.2 g, 0.0? 12 mol).

IR; (011015) 16oo cch 1585 cm ".

Ms = (m / c) 418 and 416 (rf), 5o5, 505, 215 and 215. 2- (5-Benzyloxy-4-bromophenyl) -2-methylundecane in the form of an oil (40.0 g, 82%) from 2- (4-bromo-5-hydroxyphenyl) -2-methyl- can (27.5 g, 0.115 mol).

Ia: (chois) 16o5 cch 1587 cm '“. ns; (m / c) 452 cch 450 (MÜ, 505, 505, 215 cch 215. 2- (5-Benzyloxy-4-bromophenyl) -2-methyldodecane in the form of an oil (27.5 g, 100%) of 2- (4-bromo-5-hydroxyphenyl) -2-methyl- dodecane (22.0 g, 0.0620 mol). '1 IR: (CHCl 5) 1605 and 1592 cm -1.

Ms; (m / c) 448 cch 444 (W), 505 cch 505.

Example G: 5-benzyloxy-4-bromophenol. To a slurry of 1.7 g (42.5 mmol) of potassium hydride in 55 ml of N, N-dimethylformamide, which slurry had a temperature of 0 ° C, was slowly added one solution of 7.22 g (58.2 mmol) of 4-bromoresorcinol. It is so- the kept mixture was stirred for 50 minutes, then 4.54 ml (58.2 mmol) benzyl bromide was slowly added. Reaction mixture The mixture was stirred for a further 5 hours at 0 ° C, then 200 ml cold water and 200 ml of ether were added. The ether extract washes taken with water (2 x 200 ml), dried over magnesium sulphate and evaporated to an oil. The crude oil was purified through column chromatography on 400 g of silica gel and elution was carried out with 25% ether-pentane to give 2.2 g (16%) 2,4-dibenzyloxybromobenzene, then 0.21 g (2%) 5- benzyloxy-2-bromophenol and finally 5.52 g (55%) of 5-benzylo- oxy-4-bromophenol. > 5-Benzyloxy-2-bromophenol: IR: (holes) 5521, 5221, 1610 and 1600 cm -1. hs = (m / c) 28o, 278 (MW, 189, 187 and 91). 5-Benzyloxy-4-bromophenol: m; (chciš) 5546, 5257, 1605 cch 1585 cm ".

MS: (m / cyaso, 278 (rf) and 91. f) 40 45 25 50 55 40 86 Example H: 2-Benzyloxy-4-ÅE- (5-phenylpentyloxilybromobenzene mixture of 5.50 g (42.5 mmol) of 5-benzyloxy-4-bromophenol, 5.48 g (44.4 mmol) of 2- (5-phenylpentyl) methanesulfonate and 5.47 g (57.5 mmol) anhydrous potassium carbonate in 20 ml of N, N-dimethyl- formamide was heated at 85 ° C for 6 hours, then cooled and was added to 200 ml of water and 200 ml of ether. The organic the extract was washed with water (2 x 450 ml), dried over magnesium sulfate and evaporated to an oil. This was purified by column chromatography on 400 g of silica gel and elution was performed with 2: 4 pentanzmethylene chloride. One received 4.59 g (82%) of the desired product as an oil.

IR; (CHG15) 1587 cm -1.

Ms; 426, 424, (rf), 280, 278 ccn 91.- Example I: 4-bromo-2,4-dibenzyloxybenzene. A mixture of 75.0 g (0.597 mol) 4-bromoresorcinol, 954 ml (0.8 mol) benzyl bromide and 554 g (2.4 mol) of anhydrous potassium carbonate in 400 ml of N, N- dimethylformamide was stirred for 42 hours at 2590 and for 4 hours at 85 ° C. The reaction mixture was cooled and added to 4 l of ice. 25O ml pentane-400 ml ether. The organic phase was washed with water (5 x 500 ml), dried over magnesium sulphate and evaporated to an oil. This was quickly chromatographed on 400 g of silica gel and elution were performed with 20% ether pentane. 80 g of an oil were obtained. The chromatographed the oil crystallized in pentane at 0 ° C to give 45.0 g (50%) of the title compound, m.p. 57-58 ° C.

IR: (cm -1) 1605 and 1590 cm

Ms = (m / cWO (rf), 568 cch 91.

Analysis -% C% H% Br calculated for 020114713102 65.05 4.64 24, 65 found 64.95 4.55 24.48 Example J: 2- (5-methoxyphenyl) -5-phenylpentane. A solution of 4- bromopropylbenzene (54 .mu.g) in ether (254 ml) was added dropwise during lcppcct of 2 hours to one under attcr fl ödc kckcndc mixture of magnesium (7; 52 g) in ether (78 ml). Reactional the mixture was boiled for another 50 minutes, then a solution of 5-methoxy-acetophenone (44.6 g) in ether (78 ml) added dropwise was added and the mixture was heated at reflux temperature 10 15 20 50 55 7eo90ee-2 87 for 1.5 hours. The reaction was quenched by the addition of a saturated ammonium chloride solution (254 ml), the ether phase was separated and the aqueous phase was extracted with ether (5 x 200 ml). They combined The ether extracts were dried over magnesium sulphate and evaporated vacuum, whereby an oil was obtained. This was hydrogenated in a mixture containing ethanol (500 ml), concentrated hydrochloric acid (2 ml) and 5% palladium-on-carbon (5 g). The catalyst is filtered off and the ethanol was removed in vacuo. Evaporation the residue was distilled in vacuo to give the title units.

Example K: 2- (5-hydroxyphenyl) -5-phenylpenteg. A mixture of 2- (5-methoxyphenyl) -5-phenylpentane (18.4 g) and pyridine hydrochloride chloride (94 g) was heated under nitrogen and stirring vigorously at 190 ° C for 2 hours. The reaction mixture was cooled, dissolved in 6N-H01 (200 ml) and diluted with water to 600 ml. Water- the solution was extracted with ethyl acetate (4 x 100 ml), ethyl acetate the extracts were dried over sodium sulphate and evaporated in vacuo, whereby the crude product was obtained. This was purified by chromatography. tography on silica gel.

Example L: Ethyl 5- (5-benzyloxyphenyl) crotonate (Wittig reaction). One mixture of 54-benzyloxyacetophenone (29.4 g, 0.15 mol) and carbethoxymethylenetriphenylphosphorane (90.5 g, 0.26 mol) heated was carried out under a nitrogen atmosphere at 170 ° C for 4 hours. The clear melt cooled to room temperature, triturated with ether and precipitated. the triphenylphosphine oxide was filtered off. The filtrate indunsf was taken in vacuo to give an oily residue, which was chromatographed on silica gel (1500 g). Elution carried out with benzene hexane solutions with increasingly higher benzene levels, starting with the ratio 40:60 and ending with 100% benzene. By evaporation of suitable fractions the product was obtained in the form of an oily residue.

Example M:. 5- (5-benzyloxyphenyl) butyl tosylate. A solution of ethyl 5- (5-Benzyloxyphenyl) -crotonate (1?, 8 g, 60 mmol) in ether (250 ml) was added to a mixture of lithium aluminum hydride (5.42 g, 90 mmol) and ether (250 ml). Aluminum chloride (0.18 g, 1.55 mmol) was added and the mixture was refluxed in _50 C.) : Q (Û t, - 10 45 20 25 55 Û 2 88 12 hours, after which it was cooled. Water (5.4 mL), 6N-NaOH (3.4 ml) and water (10 ml) were then added successively the reaction mixture. In this case precipitating inorganic salts was filtered off and the filtrate was evaporated in vacuo, whereby 5- (5-Benzyloxyphenyl) butanol was obtained in the form of an oil.

Tosyl chloride (11.1 g, 58.4 mmol) was added to a solution of 5- (5-benzyloxyphenyl) -4-butanol (¶44 g, 57 mmol) in pyridine (90 ml) at -45 ° C. The reaction mixture was kept at -55 ° C in 18 hours the outdoor pede then with cold 2N-H01 (15oo ml) and extracted with ether (5 x 200 ml). They combined the extracts were washed with a saturated sodium chloride solution (4 X 250 ml) the tdrkedee then over Nezsou). By in- evaporation of the dried extract, the product was obtained in the form of an oil.

Example N: 5- (5-benzyloxyphenyl) -1-phenoxybutane. A solution of phenol (4.56 g, 48.6 mmol) in dimethylformamide (40 mL) was added under a nitrogen atmosphere to a suspension of a 50% sodium hydride (2.52 g, 48.6 mmol, which sodium hydride precedes washed with pentane) in dimethylformamide (70 ml) at 60 ° C.

The reaction mixture was stirred for 1 hour at 60-70 ° C, then a solution of 5- (5-benzyloxyphenyl) butyl tosylate (18.9 g, 46 mmol) in dimethylformamide (80 ml) was added. Reaction mixture the mixture was stirred at 80 ° C for half an hour and then cooled to room temperature, diluted with cold water (2500 ml) and extracted with ether (4 x 400 ml). They combined the extracts were washed, first with cold 2N-H01 (2 x 500 ml) and then with a saturated sodium chieridine (5 x 500 ml), whereupon drying was performed with_Na2SO4. The solvent is removed under reduced pressure to give the product in shape of an oil. This was dissolved in benzene, the solution was filtered through silica gel (400 g) and the filtrate was evaporated reduced pressure, whereby the product was obtained in the form of a oil.

Example O: g 4- (5-hydroxyphenyl) -1- (4-pyridyl) pentene. A mix of 5- (5-methoxyphenyl) butyltriphenylphosphonium bromide (17.5 g, 55.4 mmol) in dimethyl sulfoxide (50 ml) was added to 4-pyridine carboxaldehyde (5.79 g, 55.4 mmol) in tetrahydrofuran (40 mL). 40 15 25 50 55 7an90ec-2 89 The mixture thus obtained was then added dropwise a slurry of 50% sodium hydride (4.87 g, 59 mmol) in tetrahydrofuran (20 ml) under a nitrogen atmosphere at 0-5 ° C, whereupon the whole was evaporated under reduced pressure. Concentric The batch was diluted with water (200 ml) and then acidified with 6N-HCl. The aqueous acidic solution was extracted with benzene (4 x 50 ml). It was then made alkaline and was extracted with benzene (5 x 50 ml). By evaporation of the combined extracts, after drying over MgSO 4, There was obtained 4- (5-methoxyphenyl) -4- (4-pyridyl) -4-pentene in the form of an oil.

By catalytic hydrogenation of the pentene thus obtained. the derivative in ethanol at a hydrogen pressure of 540 kPa in the presence of 4 g of 40% Pd / C and concentrated HCl (4 ml) were obtained. Association.

The pentane derivative thus obtained was demethylated by heating a mixture of the compound (25 mmol) and pyridine hydrochloride (55 g) under a nitrogen atmosphere at 240 ° C in 8 hours. The hot mixture was poured into water (40 ml) and the solution thus obtained was basified with 6N-NaOH. Water and pyridine was distilled off in vacuo. Ethanol (50 ml) was added to the residue and the precipitated inorganic salts are filtered off. _ rerades. The filtrate was evaporated in vacuo and the residue was chromatographed on silica gel using as eluent of 5% ethanol / benzene (4 L), 40% ethanol / benzene (4 L), 45% ethanol / benzene (4 L) and 46% ethanol / benzene (5 L).

The product was isolated by evaporation of appropriate fractions of the eluate.

There was prepared 5- (5-methoxyphenyl) butyltriphenylphosphonium the bromide by refluxing a mixture of 4- bromo-5- (5-methoxyphenyl) butane (78.5 mmol) and triphenylphosphine (785 mmol) in wlan (eo m1) in those hours. The reaction mixture was then cooled to room temperature and filtered. Filter- the cake was washed with ether and the product was dried in vacuo desiccator. 5 Example P: 5-methoxy-α-methylstyrene oxide. To a solution of dimethyl- sulfoxonium methylide (69.4 mmol) in dimethyl sulfoxide (65 mL) 5-dimethoxyacetophenone (8.55 g, was added at room temperature). vsoeoeß-2 ~ 10 15 20 50 55 90 55.5 mmol). The reaction mixture was stirred for 1 hour at 25 ° C, ice for half an hour at 50 ° C and then cooled. Among- The solution was diluted with water (50 ml) and added to one mixture of ice and water (zoo ml) - ever (250 ml) - at low temperature boiling petroleum ether (25 ml). The organic the extract was washed with water (2 x 250 ml), dried over MgSO 4 and evaporated to an oil which was subjected to fractional distillation.

Example Q: 2- (5-methoxyphenyl) -2-hydroxypropyl-2-phenylethyl ether.

A mixture of dry 2-phenylethanol (50 ml, 250 mmol) and Sodium metal (690 mg, 50 mmol) was heated at 110 ° C 50 minutes. The 1 molar solution of sodium 2-phenylecoxide is cooled to 60 ° C, 5-menoxy-u-mephylstyrene-axis (1.69 g, 10.5 mmol) was added and the reaction mixture was stirred. heated for 15 hours at 60 ° C, then cooled and set to a mixture of ether and water. The ether extract was dried over magnesium sulphate and evaporated. By vacuum distillation The excess 2-phenylethanol was removed (b.p. 65 ° C / 0.1 mm Hg). The residue was purified by column chromatography. engraving on silica gel 60 (500 g) and elution_genomf was carried out in 15 ml fractions with 60% ether-pentane, Example R: 2- (5-methoxyphenyl) propyl-2-phenylethyl ether. To one solution of 2- (5-methoxyphenyl) -2-hydroxypropyl-2-phenylethyl- ether (498 mg; 1.74 mmol) in pyridine (2 mL), which solution had a temperature of 0 ° C, phosphorus oxychloride was added dropwise (477 mL, 5.22 mmol) The temperature of the reaction mixture was rise to 20 ° C over the course of 1.5 hours. It was then stirred the reaction mixture for 1.5 hours at 20 ° C, was added to ether (150 ml) and a 15% sodium carbonate solution (100 ml). The the organic phase was separated and washed with a 1% sodium carbonate solution (5 x 50 ml), dried over magnesium sulphate and evaporated to an oil. This was dissolved in absolute ethanol (15 ml), 10% palladium-on-carbon (100 mg) was added and mixed The mixture was stirred in hydrogen gas at a pressure of 1 atmosphere. When After the hydrogen uptake had subsided, the reaction mixture was filtered through diatomaceous earth and the filtrate was evaporated to an oil. " This was purified by preparative layer chromatography on 40 45 25 50 55 vacancy I \. “I 94 silica gel plates and elution were performed twice with pentane ether 6: 4, whereby the title compound was obtained.

Example S: 2- (5-hydroxyphenyl) propyl; 2-phenylethyl ether. A mix of 2- (3-hydroxyphenyl) propyl-2-phenylethyl ether (476 mg, 0.65 mmol), pyridine (0.4 mL, 4.96 mmol) and dry pyridine chloride (4 g, 54.5 mmol) was heated at 490 ° C for 6 hours.

The reaction mixture was cooled and added to a mixture of water (400 ml) and ether (450 ml). The ether extract was washed 4 batches of water (50 ml) and together with a second ether extract (50 ml) from the aqueous phase, dried it over magnesium sulfate and evaporated to an oil. The oil was purified by preparative layer chromatography on silica gel plates and elution were performed 6 times with 50% ether pentane, whereby the title compound was obtained.

Example T: 5-methoxy-β-methylstyrene oxide. To a solution of di- phenylsulfonium methylide (4.0 mol) in tetrahydrofuran (4 liters), which solution had a temperature of -78 ° C, was added slowly 5-methoxybenzaldehyde (4.0 mol). The reaction mixture was stirred at -78 ° C for 5 hours and its temperature was then allowed rise to room temperature. The reaction mixture was added then to ether-water and the ether phase was separated, washed with water, dried over MgSO 4 and evaporated. By freight thioned distillation of the evaporation residue was obtained V headline association.

Example U: 5- (5-hydroxyphenyl) -2-propylbutyl ether. To a solution of sodium butoxide in butanol (0.5 liter 4M) was added 5-methoxy- β-methylstyrene oxide (6.55 mol). The mixture was heated to 48 ° C hours at 70 ° C, then cooled and added to a mixture of ether-water. The ether solution was separated, dried over MgSO 4 and evaporated to give the crude product 2- (5- methoxyphenyl) -5-hydroxy-2-propylbutyl ether. This was purified by column chromatography on silica gel and elution was performed with ether-pentane.

In the manner set forth in Example R, the title Association. 1 7809060-2 10 ao " 25 50 \ N '\.' 1 92 Example V: 1-bromo-5- (5-methoxyphenyl) butane. A solution of phosphorus tribromide (5.7 ml, -0.06 mol) in ether (50 ml) was added to one solution of 5- (5-methoxyphenyl) -1-butanol (50.0 g, 0.145 mol) in ether (20 ml) at a temperature between -5 ° C and -10 ° C and the reaction mixture was stirred at this temperature for 2.5 hours, after which it was warmed to room temperature and stirred for another 50 minutes. The mixture was poured onto ice (200 g) and the mixture thus obtained was extracted with ether (5 x 50 ml). The combined extracts were washed with a 5% sodium hydroxide solution (5 x 50 ml), with a saturated sodium chloride solution (4 X 50 mL) and dried over Na 2 SO 4.

The ether was distilled off in vacuo to give the title reaction. the unity that remained.

Example W: 5- (5-benzyloxy) benzyloxypropane. Sodium (0.2 mol) dissolved in n-propyl alcohol (4.0 mol) and the reaction mixture kyldee i ie = bed. Then 0.2 ml of 5-benyl oxide was added. benzyl chloride over the course of half an hour and during broken stirring. The ice bath was removed and the temperature rose eventually to the reflux temperature. After 4 hours at At this latter temperature, alcohol was distilled off. the shot under reduced pressure. The residue was treated with water for dissolving the salt present and then extraction was carried out with diethyl ether. The extract was washed with water, dried over MgSO 4 and evaporated to give received the headline association.

Example X: 6- (5-butenyl) -5-ethoxy-2-cyclohexen-4-one. A solution of 25 g (0.1 to 8 mol) of 5-ethoxy-2-cyclohexen-4-one in 25 ml of tetra- hydrofuran was added dropwise (over 50 minutes) a solution (-78 ° C) of 0.496 moles of lithium diisopropylamide (prepared prepared from 27.4 ml, 0.196 mol of diisopropylamine and 85 ml, 0.18? mol (2.2N n-butyllithium in hexane) in 125 ml of tetrahydro- furan. The reaction mixture was stirred for an additional 50 minutes. whereupon 65 ml (0.544 mol) of hexamethylphosphoramide were added successively of 58.9 ml (0.585 mol) of 4-bromo-1-butene. The reaction mixture temperature was then allowed to rise to room temperature and 10 15 20 50 55 7so9o6e-2 95 the reaction mixture was stirred for 1.5 hours, after which the reaction was stopped by the addition of 5 ml (0.277 mol) of water. The biggest the portion of the solvent was removed under reduced pressure and the residue was diluted with 1 liter of ice water and 500 ml of ether.

The ether extract was washed with water (2 x 500 ml), dried over magnesium sulphate and evaporated. By distillation of the crude oil obtained 10.1 g (29%) of the title compound.

Boiling point 85 ° C / 0.02 torr.

Example Y: 4- (5-butenyl) -2-cyclohexen-1-one. To a slurry of 1.06 g (26 mmol) of lithium aluminum hydride in 75 ml of ether, which slurry had a temperature of 0 ° C, a solution of 10 g was added (51 mmol) 6- (5-butenyl) -5-ethoxy-2-cyclohexen-1-one in 25 ml of ether.

After stirring for 1 hour, the reaction was quenched by addition of 100 ml of 2N> HCl. The mixture was stirred for 50 minutes and extruded was then rinsed with 500 ml of ether. The ether extract was washed with 250 ml of saturated sodium bicarbonate solution, dried over magnesium sulfate and evaporated.

Distillation of the crude oil gave 5.98 g (78%). by the headline association. Boiling point 155-156 ° C / 22 torr.

Example Z: 2-Benzyloxy-4- (1,1-dimethylheptyl) benzaldehyde. 2- (5- benzyloxy-4-bromophenyl) -2-methyloctane (100 g, 0.257 mol) in tetrahydrofuran (500 ml) was slowly added to magnesium powder with a particle size of 0.177 - 0.210 mm (12.5 5, 0.514 mol) at such a rate that the reflux temperature was maintained.

After the addition was complete, the reaction mixture was stirred. 2 until it has cooled to room temperature. It cools then further to 0 ° C and dimethylformamide (29.8 mL, 0.585) mol) was added dropwise over 25 minutes (reacting temperature below 10 ° C). Temperature of the reaction mixture turn was then allowed to rise and the reaction mixture was stirred in 40 minutes at room temperature. The reaction was stopped by addition of a cold, saturated aqueous solution of ammonium chloride (1800 ml) and the product was extracted with ether (1 liter).

The ether extract was washed with a saturated sodium chloride solution (2 x 1500 ml), dried over magnesium sulphate and evaporated, whereby the title compound was obtained in quantitative yield and in the form of an oil. 40 ?O 25 50 736906: -2 É eg ” IR; (onc1,), 1695, 1618 and 1580 em ““. ns; (m / e)) 55a (M *), 309, 255, 247- and 91.

In conclusion, it is emphasized that the application in addition what is stated in the claims, in particular includes: (a). Compound as defined hereinafter claim 5, wherein Z is alkylene having 8-14 carbon atoms and each of W and R are hydrogen. (b) A compound as defined in (a) above where each of R 2 and Ru is hydrogen and Z is C (CH 3) 2 (CH 2) 6. (c) A compound as defined in (b) above where R represents the formula I-B, i.e. the compound is 5-15-hydroxy-4- (1,1-dimethylheptyl) phenyl] cyclohexanol. (d) A compound as defined in (b) above where R represents the formula I-C, i.e. the compound is 5-15-hydroxy-4- (1,4-dimethylheptyl) phenyl] cycloheptanol. (e) A compound as defined in (a) above where R a is alkyl, each of R 5 and Ru is hydrogen and Z is : (cH5) Q- (cH2) 6. (f) A compound as defined in (e) above where R represents the formula I-B and R 1 is methyl, d the unit is 5-15-hydroxy-4- (1,4-dimethylheptyl) phenyl7-4-methyl- cyclohexanol. (g) A compound as defined in (a) above where R represents formula I-B, R 2 is alkenyl, R 4 is hydrogen and Z is C (CH 5) 2 - (CH 2) 6. 1 (h) A compound as defined in (g) above where H 2 is 2-propenyl, i.e. the compound is cis-5-1 4- (4,4-dimethylheptyl) phenyl} 7-trans-4-propenylcyclohexanol. (i) A compound as defined in (a) above wherein R represents formula I-B, R 4 is methyl, R 2 is hydrogen and Z is c (cH5) 2- (cH2) 7, a v s * compound is cis-5-εê-hyarOx1-4- (1,4-dimethyloctyl) phenyl7-trans-5-methylcyclohexanol. (j) 'A compound as defined below claim 2 wherein B is hydroxyl, R 4 is hydrogen, Z is (a1k 4) m -O- (alk 2) n - and W is - @ - W, I. (k) A compound as defined in (j) above where Z is -O- (alkp) -, where (alka) contains 4-5 carbon atoms, and W is fenvl; qä "O "5 Y5 1% 7so9oee-2. (1) A compound as defined in (k) above where Z is -O-CH (CH 5) (CH 2) 5 -, R represents the formula I-B and each of RE, R5 and Ru is hydrogen, i.e. the compound is 5-15 ¥ hydroxy-4- (2- (5-phenylpentyloxy) phenyl] cyclohexanol. (m) A compound as defined hereinafter claim 1, wherein R is an unsaturated cycloalkyl group. (n) A compound as defined in (m) above where B is hydroxy, each of W and Rq is hydrogen and Z is alkylene having 8-11 carbon atoms. (o) A compound as defined in (n) above where each of R 2, H 5 and RA is hydrogen and Z is C (CH 5) 2 - (CH2) 6. (p) A compound as defined in (o) above where R represents the formula I-B, i.e. the compound is 5-Hydroxy-4- (1,1-dimethylheptyl) phenyl] cyclohex-2-en-1-ol. (q) Compound as defined hereinafter claim 4 wherein R is a saturated cycloalkyl group; A and B together mans represents oxo; Z is alkylene and R 5 is hydrogen. (r) A compound as defined hereinafter claim 4 wherein Z is alkylene having 8-11 carbon atoms, each of W, R 2 and H 4 are hydrogen and X is 1 or 2. (s) A compound as defined in (r) above where R represents the formula II-B, Z is -C (CH 2) 2 (CH 2) 6, i.e. The compound is 5-N (1,1-dimethylheptyl) -2-hydroxyphenyl] cyclo- hexanone. (t) A compound as defined in (r) above wherein R represents formula II-C; Z is -C (CH 5) 2 (CH 2) 6, i.e. s The compound is 5-1β (1,1-dimethylheptyl) -2-hydroxyphenyl; 'hentenon. (u) A compound as defined in (q) above where RQ is methyl, Z is alkylene having 5-9 carbon atoms, each of R 5, R 4 and W are hydrogen and R represents formula II-B or II-C.

(V) A compound as defined in (u) above wherein R represents formula II-C; Z is C (CH 2) 9 (CH 2) 6, i.e. the compound is 5-ÅF- (1,1-dimethylheptyl) -β-hydroxyphenylph-4- methylcycloheptanone. (x) Pharmaceutical preparation as defined in wherein claim 5, wherein R is a saturated cycloalkyl group. 76 78Û906 »'2 10 '15 ? 5 50_ aä (y) Pharmaceutical preparation as defined below (X) above where each of 31, RB, R4 and W is hydrogen; H2 is hydrogen or methyl and Z is alkylene.

(Z) PHARMACEUTICAL PREPARATION AS DEFINED UNDER (y) above, wherein R represents the formula I-B or I-C and Z is alkylene having 8-11 carbon atoms. in (å) Pharmaceutical preparation as defined below (z) above, where R represents the formula I-B, Z is C (CH5) 2 (CH2) 6 and R2 are hydrogen, i.e. the compound is 5-¿Ãè (fl, 1- dimethylheptyl) -2-hydroxyphenyl7byclohexanol. _ (ä) Pharmaceutical preparation as defined in (z) above where R represents the formula I-C, Z is C (CH5), - (CH 2) 6 ooh R 2 is methyl, i.e. the compound is 5-α (1,4-di- methylheptyl) -2-hydroxyphenyl7 -4-methylcycloheptanol. (ö) Pharmaceutical preparation as defined in claim 5 wherein A and B together represent oxo. , (aa) Pharmaceutical preparation as defined in (Ö) above, where R represents the formula I-B or I-C, var and one of R 4, R 5, R 4 and W is hydrogen; R? is hydrogen or methyl and Z is alkylene. (bb) Pharmaceutical preparation as defined (aa) when above where Z is alkylene having 8-14 carbon atoms. (cc) Pharmaceutical preparation as defined in - (bb) above where R represents the formula I-B, R 1 is methyl and z is -c (cn3), (cH2) 6, a v the S compound is 5É¿š- (1,1-a methylheptyl) -β-hydroxyphenyl7-4-methylcyclohexanone. (dd) Pharmaceutical preparation as defined in - (δ) above where R represents the formula I-C; R 2 is hydrogen, Z is C (CH 3) 2 (CH 2) 6, i.e. the compound is 3-1A- (1,1-dimethyl- heptyl) -2-hydroxyphenyl7-cycloheptanone.

Claims (4)

9? A compound for use in pharmacological and medical purposes and falling within the general formula OR4 - MJ wherein R is selected from the group consisting of saturated and unsaturated cycloalkyl groups having any of the following formulas Ä E and r -fz WH »112 In where a dashed line indicates a possible further bond and where A is hydrogen; B is hydroxyl, alkanoyloxy having 1-5 carbon atoms or hydroxymethyl; or the substituents represented by A and B together form one of the following groups, namely oxo, methylene and alkylenedioxy having 2-4 carbon atoms; R 1 is selected from the group consisting of hydrogen, benzyl and alkanoyl having 1 to 5 carbon atoms; R 2 is selected from the group consisting of hydrogen, alkyl of 1-6 carbon atoms and alkenyl of 3-6 carbon atoms; R 3 is selected from the group consisting of hydrogen and methyl; R 4 is selected from the group consisting of hydrogen and alkyl of 1-6 carbon atoms, wherein R 4 is hydrogen if R 3 is methyl; Z is selected from the group consisting of (a) alkylene having 1-13 carbon atoms; (b) - (alk1) mO- (alk2) n- where each of (alk1) and (alkz) is alkylene having 1 to 13 carbon atoms wherein the sum of the carbon atoms in (alk1) and (alkz) where ; each of m and n is 0 or 1; goch W is selected from the group consisting of hydrogen, WH where W1 is selected from the group consisting of hydrogen, fluorine and chlorine; and the hemiketals of the compounds in which A and B together represent oxo and R 1 are hydrogen; and the ketals with alkanols having 1-4 carbon atoms of the compounds in which A and B together represent oxo and R 1 are hydrogen. A compound according to claim 1, wherein R is a saturated cycloalkyl group. k ä n n e t e c k n a d k ä n n e t e cgk n a d A compound according to claim 2, wherein B is hydroxyl, R 1 is hydrogen and Z is alkylene having 4-11 carbon atoms. Preferred compounds according to any one of the preceding claims, namely 5-12-hydroxy-4- (1,1-dimethylheptyl) phenylphycloheranol, 5-N-hydroxy-4- (1,1-dimethylheptyl) phenyl7bycloheptanol, 5- Alhydroxy-4- (4,1-dimethylheptyl) phenyl7F4-methyl-cyclohexanol, cis-5-12-hydroxy-4- (1,1-dimethylheptyl) phenyl] -tr-4-propenylcyclohexanol, cis-5-β2Hhydroxy 4- (1,4-dimethyloctyl) phenyl7-trans-5-methylcyclohexanol, 3- [2-hydroxy-4- (2- (5-phenylpentyloxy) phenyl] cyclohexanol, 5-12-hydroxy-4- (4,1- dimethylheptyl) phenyl7cycloher-2-en--4-ol, _3-ÄFA (1,1-dimethylheptyl) -2-hydroxyphenylybyclohexanone, 5-εE1 (1,1-dimethylheptyl) -2-hydroxyphenyl7cycloheptanone, and 5 ~ 1FL The invention relates to compounds of the general formula OR1 ZW wherein R is selected from the group consisting of saturated and 1,4-dimethylheptyl) -2-hydroxyphenyl7-4-methylcycloheptanone. unsaturated cycloalkyl groups having any of the following formulas A, BAB needle [m5 H4 1: 5 Ra IA IB ABAB OCh 5 I - 5 RR 4 2 Ra Ra Ic ID where Rq is selected from the group consisting of hydrogen, benzyl, alkanoyl having 1-5 carbon atoms, -P (0) (OH) 2 and mono- and disodium and potassium salts thereof, and -CO (CH 2) pNR 5 R 6 where p is an integer 1 -4, i.e. cycloalkanones, cycloalkanols and unsaturated analogs thereof, each having in the 3-position a 2-hydroxy-4-substituted phenyl group in which the substituent in the 4-position is an alkyl which may have a oxygen atom as part of the chain, or an aralkyl which may have an oxygen atom as part of the alkyl chain. These compounds are effective as CNS agents, in particular as analgesics, tranquilizers, sedatives and anxiolytics, and / or as anticonvulsants, diuretics and antidiarrheals for use in the treatment of mammals including humans. The invention also includes processes for the preparation of these compounds, intermediates for use in this process and the use of the compounds for pharmacological and medical purposes.