KCL-1999000269
Chemical Name: (+)-2(S)-[4-Methoxy-3-[N-[4-(trifluoromethyl)benzyl]carbamoyl]benzyl]butyric acid; alpha(S)-Ethyl-4-methoxy-3-[N-[4-(trifluoromethyl)benzyll]carbamoyl]benzenepropanoic acid
CAS No. 311769-66-1, 311769-49-0 (undefined isomer)
项目整合开发状态: Preclinical
项目研究机构: Kyorin (Originator)
合成路线:The title enantiomer has been obtained by resolution of the racemic acid (I).Acid (I) is activated as the mixed anhydride (II) with pivalic acid and triethylamine.Subsequent coupling of anhydride (II) with the potassium anion of (S)-4-benzyl-2-oxazolidinone leads to a mixture of the diastereoisomeric imides (III) and (IV),which can be separated by column chromatography and recrystallization.Then,removal of the chiral auxiliary from the target isomer (III) by hydrolysis with lithium peroxide furnishes the desired (S)-enantiomer.
📌 参考资料/链接：
参考文献标题:Enantio-dependent binding and transactivation of optically active phenylpropanoic acid derivatives at human peroxisome proliferator-activated receptor alpha
文献作者:Miyachi,H.; Nomura,M.; Tanase,T.; Suzuki,M.; Murakami,K.; Awano,K.
参考来源:Bioorg Med Chem Lett 2002,12(3),333
📄 详细内容
合成路线:In an enantioselective synthesis of the (S)-enantiomer,asymmetric alkylation of the chiral N-butyryl oxazolidinone (I) with benzyl 5-bromomethyl-2-methoxybenzoate (II) in the presence of lithium hexamethyldisilazide leads to isomer (III) in high diastereomeric excess.Subsequent benzyl ester hydrogenolysis in (III) employing Pd/C affords carboxylic acid (IV),which is further converted to the mixed anhydride (V) with ethyl chloroformate and triethylamine.Coupling of anhydride (V) with 4-trifluoromethylbenzylamine (VI) furnishes the corresponding amide (VII).The chiral auxiliary is then removed from (VII) by hydrolysis with lithium peroxide to yield the target (S)-enantiomer.
参考文献标题:Efficient asymmetric synthesis of (S)-2-ethylphenylpropanoic acid derivative,a selective agonist for human peroxisome proliferator-activated receptor alpha
文献作者:Nomura,M.; Tanase,T.; Miyachi,H.
参考来源:Bioorg Med Chem Lett 2002,12(16),2101
产品链接: CAS No. 311769-66-1››