Method of preparing .alpha.-l-aspartyl-l-phenylalanine methyl ester hydrochloride
AssigneeAjinomoto Co., Inc.
InventorsToshihisa Kato, Shinichi Kishimoto, Hideo Takeda, Mikiya Kano, Tadashi Takemoto
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Abstract
A method of preparing .varies.-L-aspartyl-L-phenylalanine methyl ester hydrochloride (.varies.-APM.HCL) from a reaction mixture of N-formyl-L-aspartic acid anhydride and L-phenylalanine methyl ester (PM), wherein .alpha.-APM.HCl is produced without isolating an intermediate by solid-liquid separation during the course of the reaction process.
Claims9
A method for preparing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride, which comprises:
- (a) adding water to an organic solvent reaction mixture containing N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester to form an aqueous layer and an organic layer, and extracting N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester into said aqueous layer, at a temperature of from 40.degree. C. to 80.degree. C.;
- (b) isolating, at a temperature from 40.degree. C. to 80.degree. C., said aqueous layer and deformylating the N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester therein by adding hydrochloric acid and methanol to said isolated aqueous layer;
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- (c) crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride salt crystals out of the mixture obtained in step (b).
A method of preparing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride, which comprises:
- (a) adding water to an organic solvent reaction mixture comprising toluene and acetic acid and containing N-formyl-.alpha.-L-aspartyl-L-phenylalanine metyl ester, and extracting N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester into said aqueous layer, at a temperature of from 40.degree. C. to 80.degree. C;
- (b) isolating, at a temperature from 40.degree. C. to 80.degree. C., said aqueous layer and deformylating the N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester therein by adding hydrochloric acid and methanol to said isolated aqueous layer;
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- (c) crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride salt crystals out of the mixture obtained in step b.
A method for preparing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride, which comprises:
- (a) adding water to an organic solvent reaction mixture comprising at least one member selected from the group consisting of N,N-dimethylformamide, acetic acid, ethylene dichloride, dichloromethane, chloroform, methyl acetate, ethyl acetate, toluene and xylene to form an aqueous layer and an organic layer, and extracting N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester into said aqueous layer, at a temperature of from 40.degree. C. to 80.degree. C.;
- (b) isolating, at a temperature from 40.degree. C. to 80.degree. C., said aqueous layer and deformylating the N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester therein by adding hydrochloric acid and methanol to said isolated aqueous layer;
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- (c) crystallizing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride salt crystals out of the mixture obtained in step (b).
Dependencies are inferred from the claim text.