Preparation and isolation of 2-methylamino-3-phenylpropanoic acid enantiomers using selective crystallization

Abstract

First, (RS)-2-chloro-3-phenylpropanoic acid [(RS)-CPP] was optically resolved using ethyl (S)-phenylalaninate as a resolving agent, aiming at preparation of optically active 2-methylamino-3-phenylpropanoic acid (MPP). The (R)-CPP obtained as the sodium salt monohydrate was reacted with methylamine to give (S)-2-methylamino-3-phenylpropanoic acid [(S)-MPP]. Next, the optical resolution of (RS)-MPP was also attempted via molecular compound formation with optically active mandelic acid (MAN). The molecular compound of (R)-MPP with (S)-MAN [(R)-MPP (S)-MAN] was obtained as the less soluble diastereomeric compound, while the (S)-MPP (S)-MAN compound was found to be the more soluble one. Recrystallization of (R)-MPP (S)-MAN compound from water, followed by treatment with acetone, gave optically pure (R)-MPP in 79% yield, based on a half amount of the starting (RS)-MPP. The (S)-MPP obtained from (S)-MPP (S)-MAN compound was again subjected to formation of molecular compound with (R)-MAN to give optically pure (S,)-MPP in 66% yield. Chirality 9:386–389, 1997. © 1997 Wiley-Liss, Inc.