By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II). The starting products are obtained as follows: a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V), which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I). b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII), which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX). The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI), which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).

By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II). The starting products are obtained as follows: a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V), which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I). b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII), which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX). The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI), which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).

By condensation of 3-(4-acetamido-2-methoxyphenoxy)propyl p-toluenesulfonate with 1-(2-fluorophenyl)piperazine (II). The starting products are obtained as follows: a) The addition of 4-acetamido-2-methoxyphenol (III) to ethyl acrylate (IV) gives ethyl-3-(4-acetamido-2-methoxyphenoxy)propionate (V), which is reduced with LiAlH4 to the corresponding alcohol and tosylated with tosyl chloride to the starting compound (I). b) The condensation of benzylamine (VI) with ethyl bromoacetate (VII) by means of K2CO3 gives N,N-bis(ethoxycarbonyl methyl)benzylamine (VIII), which is reduced with LiAlH4 and treated with SOCl2 to afford N,N-bis(2-chloroethyl)benzylamine (IX). The cyclization of (IX) with 2-fluoroaniline (X) yields 1-benzyl-4-(2-fluorophenyl)piperazine (XI), which is finally debenzylated by hydrogenation with H2 over PdIC to give piperazine (II).