PROCESS FOR PREPARING USEFUL IN SYNTHESIS OF ATORVASTATIN

摘要

A process for preparing atorvastatin as an inhibitor of HMG CoA(3-hydroxy-3-methyl-glutaryl-CoA) is provided to inhibit production of by-products, obtain high purity of intermediates, improve yield and purity of atorvastatin, and to be applicable to industry by performing reactions under mild condition. A process for preparing atorvastatin represented by the formula(1) comprises the steps of: (i) reacting cis-t-butyl-6-substituted-3,5-dihydroxy-hexanoate represented by the formula(2) with trialkylortho formate represented by CH(OR2)3 under acid catalyst to prepare cis-t-butyl-2-alkoxy-3,5-dioxane-6-substituted-hexanoate represented by the formula(3), in which R1 is nitromethane group or cyano group and R2 is C1-C6 alkyl group; (ii) reducing the nitro group or cyano group of the compound represented by the formula(3) to prepare cis-t-butyl-2-alkoxy-3,5-dioxane-7-amino-heptanoate represented by the formula(4); (iii) N-alkylation reacting the compound represented by the formula(4) with ethyl 4-fluorobenzene-2-haloacetate and isobutyryl chloride, sequentially to prepare cis-t-butyl-2-alkoxy-3,5-dioxane-6-N,N-disubstituted amino-heptanoate represented by the formula(7), in which R2 and R3 are each independently C1-C6 alkyl group and X is halogen atom; (iv) reacting the compound represented by the formula(7) with N,3-diphenylpropineamide to prepare 5-(4-fluorophenyl)-2-(1-methylethyl)-1-(cis-t-butyl-2-alkoxy-3,5-dioxane-7-amido-hetanoate)-N,4-diphenyl-1H-pyrrol-3-carboxamide represented by the formula(9); and (v) deprotecting and hydrolyzing the compound represented by the formula(9) in alcohol solvent and acid catalyst.