Preparation method of 4-methyl-5-ethoxy oxazole acid ethyl

Abstract

The invention discloses a preparation method of 4-methyl-5-ethoxy oxazole acid ethyl. The preparation method comprises the following steps of (a) adding catalytic amount of 4-dimethylamino-pyridine to a cyclization system of phosphorus oxychloride and triethylamine to carry out cyclization reaction, wherein N-ethoxy oxalyl-alpha-ethyl aminopropionic acid is taken as a raw material; (b) cooling the reaction mixture obtained in the step (a) to the room temperature and then dropwise adding the reaction mixture into deionized water for quenching reaction; and (c) carrying out separation treatment, thus obtaining the 4-methyl-5-ethoxy oxazole acid ethyl. Not only does the preparation method have the advantages of simplicity in process operation, mild reaction conditions, short reaction time, economy, environment friendliness and the like but also the purity and the molar yield of the 4-methyl-5-ethoxy oxazole acid ethyl are higher than the levels of the prior art and the 4-methyl-5-ethoxy oxazole acid ethyl meets the requirements of industrial production.

Description

technical field [0001] The invention relates to a preparation method of vitamin B6 cyclization intermediate-4-methyl-5-ethoxyoxazole ethyl ester, which belongs to the technical field of organic chemistry. Background technique [0002] 5-Alkoxy-substituted oxazole esters are important intermediates in organic chemistry and pharmaceutical synthesis. It is involved in many compounds containing the parent structure of oxazole ring, so its application range is wide and its development prospect is bright. For example, ethyl 4-methyl-5-ethoxyoxazole is an important intermediate in the synthesis and industrial production of vitamin B6, and plays a particularly important role. [0003] About the synthetic method of 4-methyl-5-ethoxy oxazole acid ethyl ester, mostly use N-alkoxy oxalyl-alpha-aminopropionic acid alkyl ester as raw material in the prior art, through dehydrating agent dehydration cyclization . The methods currently being studied are as follows: [0004] Chinese paten...

AI Technical Summary

Problems solved by technology

[0004] Chinese patent CN86101512 discloses that a kind of N-ethoxy oxalylalanine ethyl ester is carried out dehydration reaction in phosphorus oxychloride / triethylamine / toluene cyclization system to prepare 4-methyl-5-ethoxyoxine The production method of ethyl pyrenazole has a molar yield of 90%, a reaction time of up to 10 hours, and the solvent toluene used causes environmental pollution and affects the health of operators

[0005] Chinese patent CN102060801 discloses the production method of N-ethoxyoxalylalanine ethyl ester dehydration reaction in triphosgene / triethylamine / dichloromethane cyclization system, its molar yield is 81%, and the reaction time is also long Up to 9 hours, although the use of triphosgene can reduce the generation and discharge of phosphorus salts, but the total yield is low, and the reaction of raw materials is not complete

[0006] Chinese patent CN102321043 discloses a preparation method of dehydration reaction of N-ethoxyoxalylalanine ethyl ester in phosphorus oxychloride / triethylamine / dimethylformamide cyclization system, and the reaction time also needs 8 hours , the yield of the cyclization reaction has not been reported. When the inventor repeated this process, he found that the raw material conversion rate of this method was low, and there were many side reactions. There were raw materials and products that were difficult to separate, resulting in waste of raw materials and low product purity.