US Patent Number
Methods for the enantioselective synthesis of (+) and (−) lofexidine or 2-[1-(2,6)-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene involve converting (+) or (−) 1-methyl-1-[2,6-dichlorophenoxy]ethanamide to an (+) or (−) imino-ether intermediate by electrophilic attack of the amide oxygen by a trimethoxonium ion and, without isolation, converting the (+) or (−) imino-ether intermediate to (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene by adding ethylene diamine; and optionally converting the (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene into a pharmaceutically acceptable acid addition salt thereof.
University of Kentucky Research Foundation, Lexington, KY (US)
Crooks, Peter A. and Vartak, Ashish Pramod, "Enantioselective Synthesis of (+) and (–)-2-[1-(2,6-Dichlorophenoxy)-Ethyl]-1,3-Diazacyclopent-2-Ene" (2012). Pharmaceutical Sciences Faculty Patents. 6.