Patent ID: 8124790
Filing Date: 2012-02-28
Classification: A61P,C07D

Abstract:
1. A process for preparing atorvastatin comprising: i) protecting cis-t-butyl-6-substituted-3,5-dihydroxy-hexanoate of the following Chemical Formula 2 in the presence of acid catalyst with trialkyl orthoformate of the formula CH(OR wherein R ii) reducing the terminal nitro or cyano group of the cis-t-butyl-2-alkoxy-3,5-dioxane-6-substituted-hexanoate of Chemical Formula 3 to obtain cis-t-butyl-2-alkoxy-3,5-dioxane-7-amino-heptanoate of the following Chemical Formula 4: wherein R iii) N-alkylating the cis-t-butyl-2-alkoxy-3,5-dioxane-7-amino-heptanoate of Chemical Formula 4 by consecutively reacting with ethyl 4-fluorobenzene-2-haloacetate and isobutyryl chloride to obtain cis-t-butyl-2-alkoxy-3,5-dioxane-6-N,N-disubstituted amino-heptanoate of the following Chemical Formula 7: wherein R iv) cyclizing the cis-t-butyl-2-alkoxy-3,5-dioxane-6-N,N-disubstituted amino-heptanoate of Chemical Formula 7 with N,3-diphenylpropynamide to obtain 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(cis-t-butyl-2-alkoxy-3,5-dioxane-7-amido-heptanoate)-N,4-diphenyl-1H-pyrrole-3-carboxamide of the following Chemical Formula 9: wherein R v) deprotecting the 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(cis-t-butyl-2-alkoxy-3,5-dioxane-7-amido-heptanoate)-N,4-diphenyl-1H-pyrrole-3-carboxamide of Chemical Formula 9 in alcohol solvent in the presence of acid catalyst, and hydrolyzing in aqueous solution to obtain atorvastatin of the following Chemical Formula 1: wherein R