P-hydroxy phenylglycine synthesis method

Abstract

The invention discloses a p-hydroxy phenylglycine synthesis method. P-hydroxy phenylglycine is obtained by carrying out reaction of phenol and 2-hydroxy glycine in the presence of catalysts. The p-hydroxy phenylglycine synthesis method is available in raw materials, simple and convenient to operate, low in cost, high in yield and product purity, environment-friendly and suitable for commercialized production.

Description

technical field [0001] The invention relates to the synthesis of a pharmaceutical intermediate, in particular to the synthesis of an antibiotic drug intermediate, and belongs to the field of pharmaceutical chemical industry. Background technique [0002] p-Hydroxyphenylglycine is an important intermediate, and its structure is shown in formula (I). It is mainly used to synthesize the side chain of β-lactam semi-synthetic antibiotics, and can be used to produce medicines such as amoxicillin, amoxil cephalosporin, and cefoperazone. , Ceftriaxone, etc. [0003] [0004] The methods used to synthesize p-hydroxyphenylglycine mainly include the following: ① strecker amino acid synthesis method, ② hydroxymandelic acid ammonia solution method, ③ p-hydroxyphenylhydantoin hydrolysis method, ④ glyoxylic acid, phenol and active amide compound direct reaction method . [0005] The strecker amino acid synthesis method is the earliest method used to prepare p-hydroxyphenylglycine, usi...

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Problems solved by technology

[0005] The strecker amino acid synthesis method is the earliest method used to prepare p-hydroxyphenylglycine, which uses p-hydroxybenzaldehyde and cyanide to hydrolyze under acidic conditions to obtain p-hydroxyphenylglycine. The raw materials used in this method are expensive, and the yield is very low, and Requires the use of highly toxic cyanide

[0006] Hydroxymandelic acid ammonolysis method uses glyoxylic acid and phenol to make hydroxymandelic acid and then aminolysis to obtain p-hydroxyphenylglycine. The yield is low

[0007] The p-hydroxyphenylhydantoin hydrolysis method adopts the action of glyoxylic acid, urea and phenol to produce p-hydroxyphenylhydantoin and then hydrolyzes to obtain p-hydroxyphenylglycine. This method also has the disadvantages of many operation steps and low product yield

[0008] The direct reaction method of glyoxylic acid, phenol and active amido compound has few steps and low cost, and is the most used method at present. The Chinese patent with the notification number CN 101362703B discloses a synthetic method of p-hydroxyphenylglycine, which uses phenol, Glyoxylic acid and sulfamic acid are raw materials, and react in a pot under the action of catalysts such as benzenesulfonic acid, p-toluenesulfonic acid, ortho-toluenesulfonic acid, etc. The method has simple process, mild conditions and low cost, but the obtained The yield of p-hydroxyphenylglycine is low, the separation of by-products is difficult, the cost of refining is high, the amount of industrial wastewater is large, and the pressure on environmental protection is great

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