1-(1-Naphthoxy)-3-(4-substituted-piperidino)-2-propanols

#The present invention relates to a group of 1-(1-naphthoxy)-3-(4-substituted-piperidino)-2-propanols. More particularly, the present invention relates to a group of compounds having the general formula ##STR1## wherein R.sub.1 is cyano or lower alkoxycarbonyl; R.sub.2 is phenyl, p-chlorophenyl, and optionally, when R.sub.1 is cyano, R.sub.2 may be hydrogen; and R.sub.3 is hydrogen, lower alkyl or halogen.

#The lower alkoxycarbonyl groups referred to above contain 1 to 6 carbon atoms in the lower alkoxy portion and are exemplified by methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl and the like. The lower alkyl groups likewise contain 1 to 6 carbon atoms and are illustrated by methyl, ethyl, propyl, isopropyl and the like. The halogen atoms include fluorine, chlorine, bromine and iodine.

#Equivalent to the compounds of formula (I) for the purposes of this invention are the pharmaceutically acceptable acid addition and quaternary ammonium salts thereof. Such acid addition salts can be derived from a variety of organic and inorganic acids such as sulfuric, phosphoric, hydrochloric, hydrobromic, hydroiodic, sulfamic, citric, lactic, maleic, succinic, tartaric, cinnamic, acetic, benzoic, gluconic, ascorbic, and related acids. Similarly, the quaternary ammonium salts can be derived from a variety of organic esters of sulfuric, hydrohalic and aromatic sulfonic acids. Among such esters are methyl chloride and bromide, ethyl chloride, propyl chloride, butyl chloride, isobutyl chloride, benzyl chloride and bromide, phenethyl bromide, naphthylmethyl chloride, dimethyl sulfate, methyl benzenesulfonate, ethyl toluenesulfonate, ethylene chlorohydrin, propylene chlorohydrin, allyl bromide, methallyl bromide, and crotyl bromide.

#A solution of 5.0 parts of 1,2-epoxy-3-(1-naphthoxy)propane and 5.0 parts of 4-cyanopiperidine in 79 parts of ethanol is refluxed for 24 hours. The solution is then stripped of solvent under reduced pressure to give as a low melting solid, 3-(4-cyano-piperidine)-1-(1-naphthoxy)-2-propanol. The hydrochloride salt is then prepared by dissolving the solid in isopropanol and adding a solution of hydrochloric acid in isopropanol. The resulting salt is separated by filtration and crystallized from a mixture of ethanol and ethyl ether to give 3-(4-cyanopiperidino)-1-(1-naphthoxy)-2-propanol hydrochloride, melting at about 190.degree.-192.degree. C. and represented by the following structural formula ##STR5##

#To a solution of 5.0 parts of 1,2-epoxy-3-(1-naphthoxy)propane in 79 parts of ethanol is added 5.0 parts of 4-phenylpiperidine. The resulting mixture is then refluxed for 24 hours. Evaporation of the solvent from the reaction mixture under reduced pressure affords 1-(1-naphthoxy)-3-(4-phenylpiperidino)-2-propanol. This free amine is then dissolved in isopropanol and treated with a solution of hydrochloric acid in isopropanol. The resulting salt is separated by filtration and recrystallized from a mixture of ethanol and ethyl ether to give 1-(1-naphthoxy)-3-(4-phenylpiperidino)-2-propanol hydrochloride. This compound melts at 195.degree.-197.degree. C. and is represented by the following structural formula ##STR6##

#A solution of 5.0 parts of 1,2-epoxy-3-(1-naphthoxy)-propane and 5.0 parts of 4-cyano-4-phenylpiperidine in 79 parts of ethanol is refluxed for 24 hours. Evaporation of the solvent from the reaction mixture under reduced pressure affords 3-(4-cyano-4-phenylpiperidino)-1-(1-naphthoxy)-2-propanol. The hydrochloride salt is then prepared by addition of a solution of hydrochloric acid in isopropanol to an isopropanol solution of the free amine. The resulting salt is separated by filtration and recrystallized from isopropanol to afford 3-(4-cyano-4-phenylpiperidino)-1-(1-naphthoxy)-2-propanol hydrochloride, melting at 213.degree.-215.degree. C. and represented by the following structural formula ##STR7##