Synthetic method of p-hydroxyphenylglycine methyl ester

Abstract

The invention provides a synthetic method of p-hydroxyphenylglycine methyl ester. The synthetic method comprises the following steps: (1) adding D-p-hydroxyphenylglycine into methanol, conducting uniform stirring, and then dropwise adding thionyl chloride at 30-50 DEG C to obtain a methanol solution of D-p-hydroxyphenylglycine methyl ester; (2) decompressing the methanol solution of D-p-hydroxyphenylglycine methyl ester to obtain methanol under the condition that a vacuum degree is less than or equal to 0.090 MPa, then adding water, performing stirring, and carrying out decolorizing with activated carbon under an acidic condition to obtain an aqueous solution of the D-p-hydroxyphenylglycine methyl ester; and (3) dropwise adding 15-20wt% of ammonia water into the aqueous solution of D-p-hydroxyphenylglycine methyl ester to adjust a pH value to 9-10, wherein the dropwise adding time of the ammonia water is 3-6 hours, subjecting D-p-hydroxyphenylglycine methyl ester to crystallization and precipitation, and finally, carrying out centrifugal separation to obtain a D-p-hydroxyphenylglycine methyl ester product. The D-p-hydroxyphenylglycine methyl ester prepared by the method disclosed by the invention is high in recovery rate and high in purity.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical synthesis, in particular to a method for synthesizing p-hydroxyphenylglycine methyl ester. Background technique [0002] P-Hydroxyphenylglycine methyl ester is an important intermediate of antibiotics, which is used to synthesize the side chains of β-lactam semi-synthetic antibiotics. The existing preparation method of p-hydroxyphenylglycine methyl ester has problems such as long reaction time and difficult crystallization and purification of the product. Chinese patent CN111153821A discloses a preparation method of D-p-hydroxyphenylglycine methyl ester, under the condition of concentrated sulfuric acid, in the presence of concentrated sulfuric acid, under the condition of 65-80 ℃, D-p-hydroxyphenylglycine and methanol produce methyl ester reaction to obtain D-p-hydroxyphenylglycine sulfate, then distill methanol and water under reduced pressure, add D-p-hydroxyphenylglycine seed crystals ...

AI Technical Summary

Problems solved by technology

This method esterification reaction temperature is higher, easily causes the oxidation of methanol, affects the carrying out of esterification reaction; Adopt strong base such as sodium hydroxide, potassium hydroxide to adjust pH value, easily cause the hydrolysis of D-hydroxyphenylglycine crystal, reduce product recovery rate