344559-34-8Relevant articles and documents
PROCESS FOR THE SYNTHESIS OF LOFEXIDINE
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Page/Page column 14, (2021/10/22)
The present invention relates to an improved process for the synthesis of lofexidine, or a pharmaceutically acceptable salt thereof, using an aluminium alkoxide as Lewis acid.
A PROCESS FOR THE SYNTHESIS OF LOFEXIDINE
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Paragraph 4; 8-10, (2021/01/22)
Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.