【药物名称】BO-653
化学结构式(Chemical Structure):
参考文献No.56726
标题:4-Alkoxy-2,6-di-tert-butylphenol derivs.
作者:Yoshida, M.; Kato, Y.; Tamura, K.; Ohba, Y.; Cynshi, O. (Chugai Pharmaceutical Co. Ltd.)
来源:EP 0665208; US 5574178; WO 9408930
合成路线图解说明:

The condensation of 4-acetoxy-3,5-di-tert-butylphenol (I) with 2-chloro-N-(hydroxymethyl)acetamide (II) by means of H2SO4 in Ac-OH gives 4-acetoxy-3,5-di-tert-butyl-2-(2-chloroacetamidomethyl)phenol (III), which is hydrolyzed with HCl in ethanol to yield 4-acetoxy-2-/aminomethyl)-3,5-di-tert-butylphenol (IV). The oxidation of (IV) by means of hexamethylenetetramine (HMTA) affords the aldehyde (V), which is submitted to a Grignard condensation with 6-undecylmagnesium bromide (VI) in THF, followed by dehydration with conc. HCl to provide 4-acetoxy-3,5-di-tert-butyl-2-(2-pentyl-1-heptenyl)phenol (VII). The cyclization of (VII) by means of BF3/Et2O in dichloromethane gives the dihydrobenzofuran (VIII), which is finally deacetylated by reduction with LiAlH4 in THF to provide the target phenol.

参考文献No.435715
标题:Synthesis and reactivity of novel dihydrobenzofuranol antioxidants on various active oxygen species
作者:Kato, Y.; et al.
来源:17th Symp Med Chem (Nov 19 1997, Tsukuba) 1997,Abst 1-P-20
合成路线图解说明:

The condensation of 4-acetoxy-3,5-di-tert-butylphenol (I) with 2-chloro-N-(hydroxymethyl)acetamide (II) by means of H2SO4 in Ac-OH gives 4-acetoxy-3,5-di-tert-butyl-2-(2-chloroacetamidomethyl)phenol (III), which is hydrolyzed with HCl in ethanol to yield 4-acetoxy-2-/aminomethyl)-3,5-di-tert-butylphenol (IV). The oxidation of (IV) by means of hexamethylenetetramine (HMTA) affords the aldehyde (V), which is submitted to a Grignard condensation with 6-undecylmagnesium bromide (VI) in THF, followed by dehydration with conc. HCl to provide 4-acetoxy-3,5-di-tert-butyl-2-(2-pentyl-1-heptenyl)phenol (VII). The cyclization of (VII) by means of BF3/Et2O in dichloromethane gives the dihydrobenzofuran (VIII), which is finally deacetylated by reduction with LiAlH4 in THF to provide the target phenol.

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