OPTICAL RESOLUTION OF 1-(3-METHOXYPHENYL)ETHYLAMINE WITH ENANTIOMERICALLY PURE MANDELIC-ACID, AND THE CRYSTAL-STRUCTURE OF LESS-SOLUBLE DIASTEREOMERIC SALT

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 70% yield with 99% diastereomeric excess. Recrystallization of the salt from 2-propanol gave (R)-1.(R)-2 in 97% yield with 100% diastereomeric excess (total E = 68%). 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 P2(1), a = 12.642(4), b = 5.890(2), c = 10.855(4) angstrom, beta = 103.68(3)-degrees, V = 785.4(5) angstrom3, 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.