Preparation method of alpha-L-aspartate-L-phenylalanine methyl ester hydrochloride

Abstract

The invention discloses a preparation method of alpha-L-aspartate-L-phenylalanine methyl ester hydrochloride. The preparation method includes the following steps: acetic anhydride, magnesium oxide, L-aspartate and methanoic acid are sequentially mixed and then react for 5-6h at 35-50 DEG C; the temperature is reduced to 23-28 DEG C, acetic acid and L-phenylalanine are added and react for 5.5-6.5h with heat preservation, then acetic acid is replenished, the temperature is reduced to 12-18 DEG C, and filtering is conducted; and hydrochloric acid and carbinol are directly added in the filtered solid, when the temperature rises to 62-68 DEG C, the filtered solid is for hydrolysis and then for esterification for 6-8 days when the temperature is reduced to 22-28 DEG C, and finally filtering is conducted. The preparation method is high in total recovery, mild in reaction condition, capable of reducing degradation of products and large-scale production cost and shortening production process, small in the number of needed devices, easy to operate, and beneficial for large-scale production industrial production.

Description

technical field [0001] The invention belongs to the field of preparation of sweeteners, and in particular relates to a preparation method of α-L-aspartic acid-L-phenylalanine methyl ester hydrochloride. Background technique [0002] Aspartame (Aspartame, chemical name α-L-aspartate-L-phenylalanine methyl ester) is a synthetic sweetener whose sweetness is 200 times that of sucrose. Sweeteners have the advantages of pure taste, high safety, and low calories. The most commonly used route of its chemical synthesis method is to protect the amino group of L-aspartic acid and convert it into an acid anhydride, that is, formyl-L-aspartic anhydride is generated, and then condensed with L-phenylalanine methyl ester to form N -Formyl-L-aspartyl-L-phenylalanine methyl ester, and then remove the protective group and other subsequent treatments to obtain aspartame, or formyl-L-aspartic anhydride and L-phenylalanine After reaction with amino acid, carry out esterification and deprotectio...

AI Technical Summary

Problems solved by technology

But this method is for the purpose of simply improving the yield of N-formyl-L-aspartic anhydride, and does not consider N-formyl-L-aspartyl-L-phenylalanine methyl ester hydrochloride The preparation process and the influence of the preparation of N-formyl-L-aspartic anhydride on the subsequent process; When aspartic anhydride is subjected to subsequent reactions, high-temperature distillation still requires a large amount of non-recoverable solvents, produces a large number of by-products, easily causes the decomposition of N-formyl-L-aspartyl-L-phenylalanine, and reduces production costs. advanced questions

[0006] Xu Jiyang, etc. in the method of synthesizing α-L-aspartic acid-L-phenylalanine methyl ester with aspartic acid and phenylalanine as raw materials, and Chen Jinlong et al. in the study of the synthesis of aspartame , and examined a number of factors affecting the synthesis, but the steps and operations in the method are complicated, the intermediates need to be purified many times and the amount of solvent and raw materials used is large, the total yield is not high, and it is not conducive to large-scale industrial production