Optical Resolution of 1-(3-Methoxyphenyl)ethylamine with Enantiomerically Pure Mandelic Acid, and the Crystal Structure of Less-Soluble Diastereomeric Salt

Article abstract of DOI:10.1246/bcsj.66.3414

Enantiomerically pure 1-(3-methoxyphenyl)ethylamine (1), which is a key intermediate of new phenyl carbamate drugs, was obtained by a diastereomeric method with high resolution efficiency (E) by using enantiomerically pure mandelic acid (2) as a resolving agent.The first crystallization of the mixture of diastereomeric salts from methanol gave a less-soluble diastereomeric salt in 70percent yield with 99percent diastereomeric excess.Recrystallization of the salt from 2-propanol gave (R)-1*(R)-2 in 97percent yield with 100percent diastereomeric excess (total E=68percent).The crystal structure of the less-soluble diastereomeric salt, (R)-1*(R)-2, was determined by X-ray crystallography.The crystal data are: Monoclinic, space group P2₁, a=12.642(4), b=5.890(2), c=10.855(4) Angstroem, β=103.68(3) deg, V=785.4(5) Angstroem³, Z=2, R=0.058 for 1450 unique reflections.The X-ray crystallography revealed that the high resolution efficiency was due to a layer-like arrangement of the enantiomerically pure acids, of which two layers sandwiched a layer of the amines by hydrogen bonds, as well as the helical column formed by hydrogen bonds between the acids and the amines, as observed for the less-soluble diastereomeric salt of 1-phenylethylamine with mandelic acid.