BO-653
Chemical Name: 4,6-Di-tert-butyl-2,2-dipentyl-2,3-dihydrobenzofuran-5-ol
CAS No. 157360-23-1
项目整合开发状态: Phase II
项目研究机构: Chugai (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:4-Alkoxy-2,6-di-tert-butylphenol derivs.
文献作者:Yoshida,M.; Kato,Y.; Tamura,K.; Ohba,Y.; Cynshi,O.(Chugai Pharmaceutical Co.Ltd.)
参考来源:EP 0665208; US 5574178; WO 9408930
📄 详细内容
合成路线: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.
参考文献标题:Synthesis and reactivity of novel dihydrobenzofuranol antioxidants on various active oxygen species
文献作者:Kato,Y.; et al.
参考来源:17th Symp Med Chem (Nov 19 1997,Tsukuba) 1997,Abst 1-P-20
产品链接: CAS No. 157360-23-1››