Patent GB-1117758-A (GB)
Title: Naphthyloxy alkanoic acids
IPC: C07C45/63
Filed: 1965-12-06
Abstract: <FORM:1117758/C2/1> Novel compounds of the Formula I, in which R represents a cycloaliphatic radical which is either unsubstituted or substituted by one or more nuclear substituteds selected from methylene, cyanomethylene, hydroxy, halogen, C1- 5 alkyl, C2- 5 alkenyl, C2- 5 alkynyl, cyano, hydroxyalkyl, C1- 6 alkanoyl, polyfluoro substituted alkenyl, C1- 6 alkanoyloxy and oxo, R1 represents a hydrogen or halogen atom and -CnH2nrepresents a C1- 5 alkylene radical, and non-toxic, pharmacologically acceptable salts, and esters and amides thereof, are prepared by (a) reacting a naphthol of the Formula II with a di-(C1- 2 alkyl) ketone and chloroform in the presence of a base, or (b) reacting a naphthol of the Formula II with an appropriate halo substituted alkanoic acid ester and, if desired, hydrolysing the resulting ester to the free acid.  The resulting compounds of Formula I may be converted into other compounds of Formula I by conventional techniques.  For example, an oxocyloaliphatic compound may be reacted with an appropriate Grignard reagent and the resulting complex treated with aqueous ammonium chloride to form a corresponding compound containing a hydroxy group and a C1- 5 alkyl, C2- 5 alkenyl, C2- 5 alkynyl or polyfluoroalkenyl group on the same position of the cycloaliphatic ring; or an oxocyclo-alkenyl compound may be reduced with suitable reducing agents to form the corresponding hydroxy cycloalkenyl, oxocycloalkyl or hydroxycycloalkyl compounds; or a 6-(oxocycloaliphatic) - 2 - naphthyloxy - alkanoic acid alkyl ester may be reacted with triphenylphosphene-methylene or triphenylphosphinecyanomethylene to form the corresponding methylene-cycloaliphatic or cyanomethylenecycloaliphatic compounds; or a hydroxy-C2- 5 alkynyl-cyclo-aliphatic compound may be reacted (a) with mercuric oxide in an aqueous solution of sulphuric acid to form the corresponding hydroxy-acetyl-cycloaliphatic compounds, or (b) with mercuric acetate to form the corresponding acetyl-acetoxy-cycloaliphatic compounds; or a hydroxy - acetyl - cycloaliphatic compound may be reduced to form the corresponding hydroxy - (1 - hydroxyethyl) - cycloaliphatic compounds; or an oxocycloaliphatic compound may be treated with acetone cyanhydrin to form the corresponding hydroxy-cyano-cycloaliphatic compounds.  2 - Ethyl - 3 - (6 - hydroxy - 2 - naphthyl) - 2 - cyclopent-1 -one is prepared by brominating 2-acetyl -6-methoxynaphthalene to form 6-bromoacetyl - 2 - methoxynaphthalene, reacting this with ethyl butyroacetate to form ethyl 2-butyryl-3 - (6 - methoxy - 2 - naphthoyl) - propionate, heating this under nitrogen with sodium hydroxide to form 2-ethyl-3-(6-methoxy-2-naphthyl) - 2 - cyclopent - 1 - one and hydrolysing this compound.  3 - (6 - Hydroxy - 2 - naphthyl)-2,5 - dimethyl - 2 - cyclopent - 1 - one is similarly prepared using 2-methyl-3-oxovalerate instead of ethyl butyroacetate. 1 - Chloro - 6 - cyclohexyl - 2 - naphthol and 3 - (6 - hydroxy - 5 - chloro - 2 - naphthyl) cyclohexanone are prepared by reacting 6-cyclohexyl-2-naphthol and 3-(6-hydroxy-2-naphthyl) cyclohexanone, respectively, with tertiary butyl hypochlorite in carbon tetrachloride.  2 - Ethyl - 4 - methyl - 3 - (6 - hydroxy - 2 - naphthyl - 2 - cyclohexen - 1 - one is prepared by reacting 2 - propionyl - 6 - methoxy - naphthalene with dimethylamine hydrochloride and paraformaldehyde to form 2-(a -methyl-b -dimethylaminopropionyl) - 6 - methoxynaphthalene, reacting this with ethyl butyroacetate to form 2 - ethyl - 4 - methyl - 3 - (6 - methoxy - 2 - naphthyl) - 2 - cyclohexen - 1 - one and hydrolysing this compound. 2,6-Dimethyl-3-(6-hydroxy-2-naphthyl - 2 - cyclohexen - 1 - one is similarly prepared via 2,6-dimethyl-3-(6-methoxy-2-naphthyl) -2-cyclohexen-1-one.  Pharmaceutical compositions having hypo-cholesterolemic activity, for oral or parenteral administration, comprise a compound of the Formula I together with a pharmaceutical carrier.