CAS: 21498-08-8; Lofexidine Hydrochloride

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CAS号87-65-0 2,6-二氯苯酚 | CAS号78302-27-9 2-(2,6-dichloro... | CAS号107-15-3 乙二胺

📜洛非西定置于盐酸体系中,用 异丙醇 用作溶剂,化学反应生成盐酸洛非西定
参考文献:一种简单,方便,安全的盐酸洛非西定合成工艺
标题:一种简单,方便,安全的盐酸洛非西定合成工艺
摘要:提出了一种非常有效,经济且易于扩展的合成盐酸洛非西丁 ( 1 ) 的方法,该方法是一种用于治疗阿片类药物戒断的 α2-肾上腺素能受体激动剂.工艺开发允许从 2-(2,6-二氯苯氧基)丙酸乙酯 ( 13 ) 和乙二胺 ( 5 ) 在异丙醇钛的作用下,通过一锅酰胺化/咪唑啉成环反应制备盐酸洛非西丁 ( 1 ) . 所需的中间体2-(2,6-二氯苯氧基)丙酸乙酯( 13 )可以通过2-氯丙酸乙酯( 12 )对2,6-二氯苯酚( 2 )的o-烷基化反应得到.) 使用碳酸钾作为酸清除剂.
Doi:10.1021/acs.Oprd.0C00453

专利信息

专利号:US-12351558-B2
优先权日:2020-04-17
标题 :Process for the synthesis of lofexidine
发明人：NG CHOI I-TENG MONTSERRAT
权利人:MEDICHEM SA
摘要: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.

专利号:US-11459303-B2
优先权日:2019-06-21
标题 :Process for the synthesis of lofexidine
发明人：DONNOLA MONICA; BAROZZA ALESSANDRO; ROLETTO JACOPO; PAISSONI PAOLO
权利人:PROCOS SPA
摘要: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.

专利号:US-8101779-B2
优先权日:2008-10-06
标题 :Enantioselective synthesis of (+) and (–)-2-[1-(2,6-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene
发明人：CROOKS PETER A; VARTAK ASHISH PRAMOD
权利人:CROOKS PETER A; VARTAK ASHISH PRAMOD; UNIV KENTUCKY RES FOUND
摘要: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.

专利号:WO-2010016844-A1
优先权日:2008-08-08
标 题 :Lofexidine enantiomers for use as a treatment for cns disease and pathologies and its chiral synthesis
发明人：DIGENIS GEORGE A; CROOKS PETER; ALGHANANEEM ABEER
权利人:AGEAN LLC; DIGENIS GEORGE A; CROOKS PETER; ALGHANANEEM ABEER
摘要:The invention relates to methods for treatment of CNS disease and pathologies using non-racemic mixtures of lofexidine enantiomers. The invention also relates to processes for the manufacture of chirally pure enantiomers of lofexidine.

专利号:US-2011015246-A2
优先权日:2005-03-14
标题 :Lofexidine enantiomers for use as a treatment for cns disease and pathologies and its chiral synthesis
发明人：DIGENIS GEORGE; CROOKS PETER; AL-GHANANEEM ABEER
权利人:AGEAN LLC
摘要:The invention relates to methods for treatment of CNS disease and pathologies using non-racemic mixtures of lofexidine enantiomers. The invention also relates to processes for the manufacture of chirally pure enantiomers of lofexidine.

专利号:EP-3986869-B1
优先权日:2019-06-21
标 题 :A process for the synthesis of lofexidine