新产品编号:657039
Chemical Name: (Z)-2-[4-(5-Methyl-2-phenyloxazol-4-ylmethoxy)benzyloxyimino]-2-(4-phenoxyphenyl)acetic acid
CAS No. 250601-08-2, 250601-09-3 (E-isomer)
项目整合开发状态: Preclinical
项目研究机构: Takeda (Originator)
合成路线:Reduction of 4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzaldehyde (I) with NaBH4 affords alcohol (II).Subsequent chlorination of (II) employing thionyl chloride in toluene leads to the benzyl chloride (III)
合成路线:Friedel-Crafts acylation of diphenyl ether (IV) with ethyl chloroglyoxylate (V) affords the (4-phenoxyphenyl)glyoxylate (VI).This is then treated with hydroxylamine to produce a mixture of Z- and E-oximes (VII) and (VIII),which can be separated by recrystallization,followed by column chromatography.The desired Z-oxime (VII) is alkylated by the benzyl chloride derivative (III) to furnish the O-benzyl oxime (IX).Finally,saponification of the ethyl ester group of (IX) with NaOH in MeOH gives rise to the target carboxylic acid
📌 参考资料/链接：
参考文献标题:Oxyiminoalkanoic acid derivs.with hypoglycemic and hypolipidemic activity
文献作者:Kimura,H.; Momose,Y.; Odaka,H.; Sakamoto,J.; Imoto,H.(Takeda Chemical Industries,Ltd.)
参考来源:EP 1077957; JP 2000034266; JP 2000198772; US 6251926; US 6495581; WO 9958510
📄 详细内容
合成路线:Reduction of 4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzaldehyde (I) with NaBH4 affords alcohol (II).Subsequent chlorination of (II) employing thionyl chloride in toluene leads to the benzyl chloride (III)
合成路线:Friedel-Crafts acylation of diphenyl ether (IV) with ethyl chloroglyoxylate (V) affords the (4-phenoxyphenyl)glyoxylate (VI).This is then treated with hydroxylamine to produce a mixture of Z- and E-oximes (VII) and (VIII),which can be separated by recrystallization,followed by column chromatography.The desired Z-oxime (VII) is alkylated by the benzyl chloride derivative (III) to furnish the O-benzyl oxime (IX).Finally,saponification of the ethyl ester group of (IX) with NaOH in MeOH gives rise to the target carboxylic acid
参考文献标题:Studies on non-thiazolidinedione antidiabetic agents.1.Discovery of novel oxyiminoacetic acid derivatives
文献作者:Imoto,H.; Imamiya,E.; Momose,Y.; Sugiyama,Y.; Kimura,H.; Sohda,T.
参考来源:Chem Pharm Bull 2002,50(10),1349