221469-53-0Relevant academic research and scientific papers
Practical synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4- hydroxyphenyl)hexanoic acid: A key intermediate for a therapeutic drug for neurodegenerative diseases
Ito, Tatsuya,Ikemoto, Tomomi,Yamano, Toru,Mizuno, Yukio,Tomimatsu, Kiminori
, p. 3525 - 3531 (2003)
A practical method for the preparation of (R)-(+)-6-(1,4-dimethoxy-3- methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid (R)-2, a key intermediate for a therapeutic drug for neurodegenerative diseases, has been developed. rac-Methyl 6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-(propionyloxy)phenyl) hexanoate rac-9b was synthesized from 2-methylnaphthoquinone in seven steps. An optically active ester (R)-9b was readily obtained from the corresponding racemic ester by lipase-catalyzed resolution, followed by sulfation or phosphorylation. Sulfation by a sulfur trioxide pyridine complex or phosphorylation by phosphoryl chloride enabled facile isolation of the optically active ester simply by extraction. Optically active acid (R)-2 was synthesized in excellent enantiomeric excess by hydrolysis of (R)-9b followed by recrystallization. The present synthesis of (R)-2 was accomplished in 10 steps without requiring chromatographic purification.
