Cetamolol hydrochloride, ICI-72222(free base), AI-27303
2-[2-[3-(叔丁基氨基)-2-羟基丙氧基]苯氧基]-N-甲基乙酰胺盐酸盐 塞他洛尔 Chemical Name: (?-2-[o-[3-(tert-Butylamino)-2-hydroxypropoxy]phenoxy]-N-methylacetamide hydrochloride; (?-2-[2-[3-[(1,1-Dimethylethyl)amino]-2-hydroxypropoxy]phenoxy]-N-methylacetamide hydrochloride
CAS No. 77590-95-5, 34919-98-7 (free base)
项目整合开发状态: Phase III
项目研究机构: AstraZeneca (Originator)
合成路线:The condensation of 2-(N-methylcarbamoylmethoxy)phenol (I) with 3-benzyloxy-1-(p-toluenesulfonyloxy)-2-propanol (II) by means of Na in refluxing methoxyethanol gives 3 benzyloxy-1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2-propanol (III),which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol yielding 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2,3-propanediol (IV).The tosylation of (IV) with tosyl chloride in pyridine affords 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-3-tosyloxy-2-propanol (V),which by treatment with NaOH in water is converted into 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2,3-epoxypropane (VI).Finally,this compound is treated with tertbutylamine in refluxing tert-butanol.
📌 参考资料/链接：
参考文献标题:Cetamolol hydrochloride
文献作者:Hillier,K.; Castar,J.; Blancafort,P.; Serradell,M.N.
参考来源:Drugs Fut 1983,8(4),305
📄 详细内容
合成路线:The condensation of 2-(N-methylcarbamoylmethoxy)phenol (I) with 3-benzyloxy-1-(p-toluenesulfonyloxy)-2-propanol (II) by means of Na in refluxing methoxyethanol gives 3 benzyloxy-1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2-propanol (III),which is debenzylated by hydrogenolysis with H2 over Pd/C in methanol yielding 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2,3-propanediol (IV).The tosylation of (IV) with tosyl chloride in pyridine affords 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-3-tosyloxy-2-propanol (V),which by treatment with NaOH in water is converted into 1-[2-(N-methylcarbamoylmethoxy)phenoxy]-2,3-epoxypropane (VI).Finally,this compound is treated with tertbutylamine in refluxing tert-butanol.
参考文献标题:
文献作者:Tucker,H.
参考来源:FR 2250752
产品链接: CAS No. 77590-95-5›› 产品链接: CAS No.34919-98-7››