Butofilolol, CM-6805, Cafide-药物合成数据库

【药物名称】Butofilolol, CM-6805, Cafide

化学结构式(Chemical Structure):

参考文献No.	199366
标题:	Butofilolol
作者:	Casta馿r, J.; Blancafort, P.; Serradell, M.N.; Neuman, M.
来源:	Drugs Fut 1982,7(2),96

合成路线图解说明: The reaction of 5-fluorosalicylaldehyde (I) with 1-chloro-3-(tert-butylamino)-2-propanol (II) by means of p-toluenesulfonic acid in refluxing benzene gives 5-chloromethyl-3-(tert-butyl)-2-(2-hydroxy-5-fluorophenyl)oxazolidine (III), which is cyclized again by treatment with NaH in hot DMF to afford 8-aza-4,9-dioxa-11-fluoro-8-(tert-butyl)-2,3-benzobicyclo[4.2.1]octan (IV). Hydrolysis of (IV) with aqueous 1N HCl at 80 C yields 1-(2-formyl-4-fluorophenoxy)-3-(tert-butylamino)-2-propanol (V), which is submitted to a Grignard reaction with propylmagnesium bromide (A) in refluxing ether to afford 1-[2-(1-hydroxybutyl)-4-fluorophenoxy]-3-(tert-butylamino)-2-propanol (VI). Finally, this compound is oxidized with chromic acid in acetone - H2SO4.

参考文献No.	700782
标题:	Compositions for treatment of cardiovascular conditions associated with overproduction of catecholamines
作者:	Demarne le Florence, H.
来源:	BE 0830766; CA 1052820; DE 2528147; FR 2276032; GB 1501632; JP 51023233; NL 7507703; US 4252825; US 4302601

合成路线图解说明: The reaction of 5-fluorosalicylaldehyde (I) with 1-chloro-3-(tert-butylamino)-2-propanol (II) by means of p-toluenesulfonic acid in refluxing benzene gives 5-chloromethyl-3-(tert-butyl)-2-(2-hydroxy-5-fluorophenyl)oxazolidine (III), which is cyclized again by treatment with NaH in hot DMF to afford 8-aza-4,9-dioxa-11-fluoro-8-(tert-butyl)-2,3-benzobicyclo[4.2.1]octan (IV). Hydrolysis of (IV) with aqueous 1N HCl at 80 C yields 1-(2-formyl-4-fluorophenoxy)-3-(tert-butylamino)-2-propanol (V), which is submitted to a Grignard reaction with propylmagnesium bromide (A) in refluxing ether to afford 1-[2-(1-hydroxybutyl)-4-fluorophenoxy]-3-(tert-butylamino)-2-propanol (VI). Finally, this compound is oxidized with chromic acid in acetone - H2SO4.