Patent ID: 6765100
Filing Date: 2004-07-20
Classification: C07B,C07C,C07D

Abstract:
A method for producing an N-carbamate-protected &bgr;-aminoepoxide crystal, comprising:(a) dissolving N-carbamate-protected &bgr;-aminoalcohol comprising at least a diastereomer thereof as an impurity and being represented by the formula (1), in at least one solvent selected from the group consisting of aromatic hydrocarbon, aryl halide, cyclohexane, aqueous mixture, acetone and 2-propanol, to remove insoluble material: wherein in formula (1): R represents a lower alkyl group, benzyl group or fluorenylmethyl group; A represents an unsubstituted or substituted alkyl group with 1 to 10 carbon atoms, an unsubstituted or substituted aryl group with 6 to 15 carbon atoms or an unsubstituted or substituted aralkyl group with 7 to 20 carbon atoms, or a group containing one or more hetero atoms in the carbon backbone; X represents halogen atom; * represents asymmetric carbon atom; and wherein the steric configuration at 2- and 3-positions is (2R, 3S) or (2S, 3R); and said diastereomer which exists as an impurity has a steric configuation of (2R, 3R) or (2S, 3S); (b) treating the N-carbamate-protected &bgr;-aminoalcohol represented by the formula (1) with a base, thereby converting the N-carbamate-protected &bgr;-aminoalcohol to N-carbamate-protected &bgr;-aminoepoxide represented by the formula (2): wherein in formula (2), R, A and * have the same meanings as recited above; and wherein the steric configuration at 2- and 3-positions is (2R, 3S) or (2S, 3R) and wherein said N-carbamate-protected &bgr;-aminoepoxide represented by formula (2) comprises as an impurity a diastereomer having the configuration of (2R, 3R) or (2S, 3S); (c) treating the N-carbamate-protected &bgr;-aminoepoxide comprising at least a diastereomer thereof as an impurity and being represented by the formula (2) with an acid, thereby converting the diastereomer which has the configuration of(2R, 3R) or (2S, 3S) to an oxazolidin-2-one derivative represented by the formula (3): wherein in formula (3), A and * have the same meaning as recited above; and wherein the steric configuration at 4- and 5-positions is (4S, 5R) or (4R, 5S), and optionally separating and removing the resulting oxazolidin-2-one derivative in water or an aqueous mixture solvent; and (d) crystallizing the N-carbamate-protected aminoepoxide represented by the formula (2) in an aqueous mixture solvent, to obtain crystals of said N-carbamate-protected aminoepoxide having the configuration (2R, 3S) or (2S, 3R).