PIPERAZINE SALT AND A PROCESS FOR THE PREPARATION THEREOF

摘要

592907 Disclosed is a process for the preparation of trans N-{ 4-{ 2-[4-(2,3-dichlorophenyl)-piperazine-1-il]-ethyl} -cyclohexylamine dihydrochloride monohydrate wherein a) reacting trans 2-{ 1-[4-(N-tert-butoxycarbonyl)amino]-cyclohexyl} -acetic acid ester with sodium borohydride and aluminium trichloride to give trans 2-{ 1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl} -ethanol; b) reacting trans 2-{ 1-[4-(N-tert-butoxycarbonyl)-amino]cyclohexyl} -ethanol obtained with methanesulfonic acid chloride in the presence of an acid binding agent to give trans 2-{ 1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl} -ethyl methanesulfonate; c) reacting trans 2-{ 1-[4-(N-tert-butoxycarbonyl)-amino]-cyclohexyl} -ethyl methanesulfonate obtained with 2,3-dichlorophenyl-piperazine in the presence of an acid binding agent to give trans N-{ 4-{ 2-[4-(2,3-dichlorophenyl)piperazine-1-il]-ethyl} -cyclohexylamine; d) heating trans N-{ 4-{ 2-[4-(2,3-dichlorophenyl)piperazine-1-il]-ethyl} -cyclohexylamine obtained to a temperature between 40-100?C in a mixture of aqueous hydrochloric acid/methanol to give trans N-{ 4-{ 2-[4-(2,3-dichlorophenyl)piperazine-1-il]-ethyl} -cyclohexylamine dihydrochloride monohydrate. Also disclosed is Trans N-{ 4-{ 2-[4-(2,3-dichlorophenyl)-piperazine-1-il]-ethyl} -cyclohexylamine dihydrochloride monohydrate.