合成路线1

This compound has been obtained by three related ways: 1.- The Grignard condensation of ethyl cyclohexanecarboxylate (I) with benzylmagnesium bromide (II) in THF gives 1-cyclohexyl-2-phenylethanone (III), which is condensed with bromoacetaldehyde diethyl acetal (IV) by means of potassium tert-butoxide in DMSO to yield 4-cyclohexyl-4-oxo-3-phenylbutyraldehyde diethylacetal (V). The methylation of (V) by means of methyl iodide and potassium tert-butoxide in the same solvent affords 4-cyclohexyl-3-methyl-4-oxo-3-phenylbutyraldehyde diethylacetal (VI), which is treated with HCl in acetone to give the corresponding aldehyde (VII). The reductocondensation of (VII) with 1-(2-methoxyphenyl)piperazine (VIII) by means of sodium triacetoxyborohydride in dichloromethane/acetic acid yields 1-cyclohexyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-methyl-2-phenyl-1-butanone (X) as a racemic mixture, which is resolved by chiral chromatography over a Chiralpak AD column. 2.- The Grignard condensation of 2-phenylpropionaldehyde (XI) with cyclohexylmagnesium chloride (XII) in ethyl ether/THF gives 1-cyclohexyl-2-phenyl-1-propanol (XIII), which is oxidized with DMSO and P2O5 in dichloromethane yielding the corresponding ketone (XIV). The condensation of (XIV) with allyl bromide by means of potassium tert-butoxide in THF affords 1-cyclohexyl-2-methyl-2-phenyl-4-penten-1-one (XV), which is ozonolyzed with O3 in methanol catalyzed by a small amount of Sudan III affording the previously reported aldehyde (VII). 3.- The condensation of aldehyde (VII) with 1-(2-methoxyphenyl)piperazine (VIII) can also be performed in isopropyl acetate giving 1-cyclohexyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-methyl-2-phenyl-3-buten-1-one (IX), which is hydrogenated with H2 over Pd/C in isopropanol to afford the previously reported racemic mixture (X).