Mabuterol hydrochloride, KF-868DS, PB-868, Broncholin
马布台诺 甲醇中马布特罗盐酸盐(以马布特罗计)Chemical Name: 1-[4-Amino-3-chloro-5-(trifluoromethyl)phenyl]-2-(tert-butylamino)ethanol hydrochloride
CAS No. 56795-19-8, 56341-08-3 (free base), 54240-36-7 (monoHCl)
项目整合开发状态: Launched-1986
项目研究机构: Boehringer Ingelheim (Originator), Kaken (Licensee)
合成路线:Chlorination of 4-amino-3-trifluoromethylbenzoic acid (I) gives 4-amino-3-chloro-5-trifluoromethylbenzoic acid (II),which is transformed in two steps to 4'-amino-3'-chloro-5'-trifluoromethylacetophenone (IV) by means of its acid chloride (III) and diethyl malonate.UV-catalyzed bromination with bromine in glacial acetic acid at 60-65 C gives the corresponding alpha-bromoketone (V).Reaction of (V) with tert-butylamine in isopropanol at 20 C leads to 4'-amino-2-tert-butylamino-3'-chloro-5'-trifluoromethylacetophenone (VI),which,without isolation,is reduced with sodium borohydride to the base (VII) of the title compound.The latter is obtained by treatment of (VII) with hydrochloric acid in diethyl ether.The optical isomers of mabuterol have been separated via the diastereomeric esters obtained by treating the racemate with (-)-methoxvcarbonyl chloride.
📌 参考资料/链接：
参考文献标题:Mabuterol Hydrochloride
文献作者:Kr黦er,G.; Engelhardt,G.
参考来源:Drugs Fut 1985,10(11),913
📄 详细内容
合成路线:Chlorination of 4-amino-3-trifluoromethylbenzoic acid (I) gives 4-amino-3-chloro-5-trifluoromethylbenzoic acid (II),which is transformed in two steps to 4'-amino-3'-chloro-5'-trifluoromethylacetophenone (IV) by means of its acid chloride (III) and diethyl malonate.UV-catalyzed bromination with bromine in glacial acetic acid at 60-65 C gives the corresponding alpha-bromoketone (V).Reaction of (V) with tert-butylamine in isopropanol at 20 C leads to 4'-amino-2-tert-butylamino-3'-chloro-5'-trifluoromethylacetophenone (VI),which,without isolation,is reduced with sodium borohydride to the base (VII) of the title compound.The latter is obtained by treatment of (VII) with hydrochloric acid in diethyl ether.The optical isomers of mabuterol have been separated via the diastereomeric esters obtained by treating the racemate with (-)-methoxvcarbonyl chloride.
参考文献标题:Synthesis of futher amino-halogen substituted phenylaminoethanols
文献作者:Kr黦er,G.; Keck,J.; Noll,K.; Pieper,H.
参考来源:Arzneim-Forsch Drug Res 1984,34(11a),1612
产品链接: CAS No.56341-08-3›› 产品链接: CAS No.54240-36-7››