丁酸氯维地平降解杂质的合成

以4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸(2-氰基乙基)（甲基）酯(5)为起始原料，合成了丁酸氯维地平的5种降解杂质：4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯(A)， 4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3-吡啶羧酸甲酯(B)， 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸单甲酯(C)， 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸（丁酰氧基甲基）（甲基）酯(D)和4-(2,3-二氯苯基)-2,6-二甲基-3-吡啶羧酸甲酯(E)。其中A由5水解制得；B由A脱羧制得；C由5氧化后再经水解制得；D由C和丁酸氯甲酯缩合制得；E由C脱羧制得，化合物结构经¹H NMR和MS（ESI）确证。

Synthesis of The Degradation Impurities of Clevidipine Butyrate

Five degradation impurities of clevidipine butyrate, 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid monomethyl ester(A), 4-(2,3-dichlorophenyl)-1,4-di-hydro-2,6-dimethy-3-pyridinecarboxylic acid methyl ester(B), 4-(2,3-dichlorophenyl)-2,6-dimethyl-3,5-pyridnedicarboxylic acid monomethyl ester(C), 4-(2,3-dichlorophenyl)-2,6-dimethyl-3,5-pyr-idinedicarboxylic acid methyl(1-oxobutoxy) methyl ester( D) and 4-(2,3-dichlorophenyl)-2,6-dime-thyl-3-pyridinecarboxylic acid methyl ester(E), were synthesized using 4-(2,3-dichlorophenyl)-1,4-dihydro-2 ,6-dimethyl-3 ,5-pyridinedicarboxylic acid ( 2-cyano-ethyl ) methyl ester ( 5 ) as the starting material. A was synthesized by hydrolysis of 5, B was prepared by decarboxylation of A, C was synthe-sized by the hydrolysis after oxidation of 5 , D was the condensation product of C and chloromethyl bu-tyrate, and E was directly prepared by decarboxylation of C. The structures were confirmed by 1 H NMR and MS( ESI) .