- An Easy, Convenient, and Safe Process for the Synthesis of Lofexidine Hydrochloride
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A very efficient, cost-effective, and easily scalable process for the synthesis of lofexidine hydrochloride (1), an alpha 2-adrenergic receptor agonist used for treating opioid withdrawal is presented. Process development allows the preparation of lofexidine hydrochloride (1) through a one-pot amidation/imidazoline ring formation reaction, starting from ethyl 2-(2,6-dichlorophenoxy)propionate (13) and ethylenediamine (5) by the action of titanium isopropoxide. The required intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (13) can efficiently be obtained through O-alkylation of 2,6-dichlorophenol (2) with ethyl 2-chloropropionate (12) using potassium carbonate as an acid-scavenger agent.
- Donnola, Monica,Airoldi, Annalisa,Barozza, Alessandro,Roletto, Jacopo,Paissoni, Paolo
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p. 1816 - 1821
(2021/08/18)
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- PROCESS FOR THE SYNTHESIS OF LOFEXIDINE
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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.
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Page/Page column 15
(2021/10/22)
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- A PROCESS FOR THE SYNTHESIS OF LOFEXIDINE
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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.
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Page/Page column 4; 11-13
(2021/01/22)
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- A scalable, enantioselective synthesis of the r2-adrenergic agonist, lofexidine
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A scalable and high-yielding synthetic route toward pure enantiomers of the α2-adrenergic agonist, lofexidine hydrochloride, is presented. Salient features include a rapid one-pot amide alkylation-imidazoline formation sequence on the carboxami
- Vartak, Ashish P.,Crooks, Peter A.
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body text
p. 415 - 419
(2010/04/22)
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- Feed additive for improving growth in agricultural animals
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By using α-mimetics, particularly compounds of general formulae I to III and the compounds listed in Table I, as feed additives in fattening animals, it has surprisingly been possible to improve the daily weight gain, the utilisation of fodder and the ratio of muscle to fat in favor of the proportion of muscle and protein.
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- Process for producing (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene
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This invention relates to processes for producing the (-)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene and to pharmaceutically acceptable acid addition salts thereof and the method for lowering the blood pressure in human beings suffering from increased blood pressure, using these compounds.
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- (+)-2-[1-(2,6-Dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene and the method for the treatment of human beings suffering from nervous disarrangements, in particular migraine
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This invention relates to (+)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene and to pharmaceutically acceptable acid addition salts thereof and the method for the treatment of human beings suffering from nervous disarrangements, in particular migraine, using these compounds.
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- Chemistry of Lofexidine
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The systematic syntheses and pharmacological studies of numerous imidazolines aryloxyalkyl-substituted in the 2-position show that substitution of the aryl residue in the 2,6-position by halogen and addition of a side-chain to the alkyl residue results in compounds with marked antihypertensive activity. 2-[1-(2,6-Dichlorphenoxy)-ethyl]-2-imidazoline hydrochloride (lofexidine, Lofetesin and Loxacor) exhibits the most marked hypotensive activity. The synthesis and physico-chemical properties of lofexidine are described.
- Betzing,Biedermann
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p. 916 - 918
(2007/10/02)
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