Chlorocitrate, Ro-21-7716

(1R,2R)-1-氯-2-羟基丙烷-1,2,3-三羧酸Chemical Name: (1R,2R)-1-Chloro-2-hydroxy-1,2,3-propanetricarboxylic acid; (-)-threo-Chlorocitric acid
CAS No. 76432-78-5
项目整合开发状态: Biological Testing
项目研究机构: Roche (Originator)
合成路线:The dipotassium salt of trans-aconitic acid (I) is oxidized in aqueous solution at low temperature using KOCl to give the tripotassium salt of (+)-threo-chlorocitric acid (II),which is converted in situ to (+)-threo-epoxyaconitic acid,tripotassium salt (III) with the addition of KOH.This material is isolated from the reaction mixture as its monopotassium salt (IV),which crystallizes from solution after the addition of two equivalents of HCl.The monopotassium salt is then treated with one equivalent of H2SO4 in acetone yielding (+)-threo-epoxyaconitic acid (V),which in turn is resolved via its bis((S)-alpha-methyl-p-nitrobenzylamine salt) (VI).The salt is split using ethereal HCl or HCl in ethyl acetate yielding (+)-threo-epoxyaconitic acid (VII).Treatment of (VII) with HCl and NaCl in aqueous solution at 70 C furnishes (+)-threo-chlorocitric acid,which,after isolation from the reaction mixture,is purified by crystallization from acetonitrile.