文献类型：专利

英文题名：Preparation of valsartan involves reacting bromine-containing biphenyl compound with sodium methoxide in methyl alcohol, dissolving obtained compound in methylene chloride, adding 2,3-dichloro-5.6-dicyanobenzoquinone, and reacting

作者：LU L;PAN C;WANG T;WANG Q;YU X;FENG C;YUAN Y

机构：[1]UNIV EAST CHINA SCI & TECHNOLOGY

申请号：CN104292174-A

申请日：2014-10-08

公开日：2015-01-21

语种：英文

收录：DERWENT

摘要：NOVELTY - Valsartan is prepared by (1) reacting bromine-containing biphenyl compound with sodium methoxide in methyl alcohol, (2) dissolving obtained compound in methylene chloride, adding 2,3-dichloro-5.6-dicyanobenzoquinone (DDQ), reacting, (3) adding obtained compound and L-valine methyl ester hydrochloride in anhydrous dichloromethane, stirring, adding sodium cyanoborohydride, reacting, (4) adding obtained compound in toluene solvent, adding triethylamine and n-pentanoyl n-pentyl chloride, reacting, (5) adding obtained compound and aqueous monopotassium phosphate solution in acetonitrile, and refluxing. USE - Preparation of valsartan (claimed). ADVANTAGE - The preparation avoids strong alkaline material which produces racemization and maintains optical product purity. DETAILED DESCRIPTION - Valsartan of formula (VII) is prepared by (1) reacting bromine-containing biphenyl compound of formula (I) with sodium methoxide in methyl alcohol at room temperature to obtain biphenyl compound of formula (II), (2) dissolving obtained compound in methylene chloride, adding DDQ, reacting to obtain biphenylaldehyde compound of formula (III), (3) adding obtained compound and L-valine methyl ester hydrochloride in anhydrous dichloromethane, stirring for 10-60 minutes, adding sodium cyanoborohydride, reacting to obtain biphenyl compound of formula (IV), (4) adding obtained compound in toluene solvent, continuously adding triethylamine and n-pentyl chloride at 0-20 degrees C, reacting to obtain biphenyl compound of formula (V), (5) adding obtained compound and aqueous monopotassium phosphate solution in acetonitrile, refluxing to obtain biphenyl-containing compound of formula (VI), (6) adding obtained compound in toluene, adding aqueous sodium hydroxide solution, completing reaction, and acidifying.