AN IMPROVED PROCESS FOR SYNTHESIS OF PYRROLE DERIVATIVE, AN INTERMEDIATE FOR ATORVASTATIN

摘要

The present invention also relates to a novel impurity, (6-{2-[2-(6-{2-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-ethyl }-2,2-dimethyl-[1,3]-dioxan-4-yl)-acetylamino]-ethyl}-2,2-dimethyl-[1,3]-dioxan-4-yl)-acetic acid tert-butyl ester, the compound of formula IV, having the following structure: The present invention also provides methods of preparing the compound of formula rv as well as methods of using the compound of formula IV as a reference marker and a reference standard. The present invention also provides an improved process for preparing (4R,cis)-6-[2- [3-phenyl-4-(phenyl-carbamoyl)-2-(4-fluorophenyl)-5-(1-methyl-ethyl)-pyrrole-1-yl]- 2,2-dimethyl-[1,3] dioxane-4-yl-acetic acid-tertiary butyl ester, the compound of formula I, said process comprising the step of condensing 4-fluoro-a-[2-methyl-1- oxopropyl]-?-oxo-N,ß-diphenylbenzene butanamide, the compound of formula III, with (4R,Cis)-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4- acetate, the compound of formula II, in the presence of a catalytic amount of an acid in the presence of a solvent system, preferably a binary solvent system, to obtain the desired compound (4R,cis)-6-[2-[3-phenyl-4-(phenyl-carbamoyl)-2-(4-fluorophenyl)- 5-(1-methyl-ethyl)-pyrrole-1-yl]-2,2-dimethyl-[1,3] dioxane-4-yl-acetic acid-tertiary butyl ester.