Optical resolution by preferential crystallization of (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid and its use in synthesizing optically active 2-amino-2-methyl-3-phenylpropanoic acid.
To synthesize optically active 2-amino-2-methyl-3-phenylpropanoic acid (1), (RS)-2-benzoylamino-2-benzyl-3-hydroxypropanoic acid [(RS)-2] was first optically resolved using cinchonidine as a resolving agent to yield optically pure (S)- and (R)-2 in yields of about 70%, based on half of the starting amount of (RS)-2. Next, the racemic structure of (RS)-2 was examined based on melting point, solubility, IR spectrum, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-2. Results indicated that the (RS)-2 exists as a conglomerate at room temperature, although it forms a racemic compound at the melting point. The optical resolution by preferential crystallization yielded (S)- and (R)-2 with optical purities of about 90%, which were fully purified by recrystallization. After O-tosylation of (S)- and (R)-2, reduction by zinc powder and sodium iodide gave (R)- and (S)-1, respectively.
Shiraiwa
Tadashi
T
Unit of Chemistry, Faculty of Engineering and High Technology Research Center, Kansai University, Suita, Osaka, Japan. shiraiwa@ipcku.kansai-u.ac.jp
Suzuki
Masahiro
M
Sakai
Yoshio
Y
Nagasawa
Hisashi
H
Takatani
Kazuhiro
K
Noshi
Daisuke
D
Yamanashi
Kenji
K
D003460:Crystallization; D009904:Optical Rotation; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry*
D010666:Phenylpropionates