PREPARATION METHOD OF DEXMEDETOMIDINE INTERMEDIATE

摘要

The present invention discloses a preparation method of 2,3-dimethyl phenyl-1-trityl-imidazole-4-ketone. In accordance with this method, imidazole-4-ethyl formate is used as a raw material; ethyl formate is used for amino protection, 1-trityl-1H-imidazole-4-formic acid is obtained after basic hydrolysis; 1-trityl-1H-imidazole-4-formic acid and N,O-dimethylhydroxylamine hydrochloride are subjected to condensation so as to obtain N-methoxyl-N-methyl-1-trityl-1H-imidazole-4-formamide; and N-methoxyl-N-methyl-1-trityl-1H-imidazole-4-formamide and a Grignard reagent prepared by the reaction of 2,3-dimethylbromobenzene with magnesium are subjected to a Grignard reaction, and then the target product 2,3-dimethyl phenyl-1-trityl-1H-imidazole-4-ketone is obtained. Compared with the reported preparation methods, the preparation method is more convenient to operate and is beneficial for industrial production.

主权项

1. A preparation method of dexmedetomidine intermediate, characterized in that, said preparation method comprises the following steps in turn:
1) taking triethylamine as an alkaline protonation reagent, performing amino protection on imidazole-4-ethyl formate by using triphenylchloromethane to generate 1-trityl-1H-imidazole-4-ethyl formate; 2) hydrolyzing 1-trityl-1H-imidazole-4-ethyl formate in alkaline liquor, then performing acid precipitation to obtain 1-trityl-1H--imidazole-4-formic acid; 3) with the existence of a condensation reagent and under alkaline conditions, performing condensation on 1-trityl-1H-imidazole-4-formic acid and N,O-dimethylhydroxylamine hydrochloride to generate N-methoxyl-N-methyl-l-trityl-1H-imidazole-4-formamide; 4) preparing Grignard reagent, 2,3-dimethyl phenyl magnesium halide, through reaction between 2,3-dimethylhalobenzene and magnesium; 5) performing Grignard reaction between N-methoxyl-N-methyl-1-trityl-1H-imidazole-4-formamide and 2,3-dimethyl phenyl magnesium halide to generate 2,3 -dimethyl phenyl- 1 -trityl- 1H-imidazole-4-ketone.