盐酸巴尼地平的合成

Synthesis of Barnidipine Hydrochloride

以3-羟基丙腈、2,2,6-三甲基-4H-1,3-二氧环己烯-4-酮、3-硝基苯甲醛、β-氨基巴豆酸甲酯为原料,经Hantzsch反应、选择性水解、奎尼丁拆分得中间体(R)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸;另外,以反式-4-羟基-L-脯氨酸为原料,经脱羧、苄基化、Mitsunobu反应、水解反应得中间体(S)-3-羟基-1-苄基吡咯烷;两个中间体经缩合得盐酸巴尼地平,纯度99.3%,ee值99.45%,总收率10%。

（R） -2,6-Dimethyl-4- （3-nitrophenyl） -5- （methoxycarbonyl） - 1,4-dihydropyridine-3-carboxylic acid, a key intermediate of barnidipine, was synthesized from 3-hydroxylpropionitrile, 2,2,6-trimethyl-4H-1,3- dioxin-4-one, 3-nitrobenzaldehyde and methyl 3-aminobut-2-enoate via Hantzsch condensation, selective hydrolysis and resolution with quinidine. Another crucial intermediate （S） -1-benzyl-3-pyrrolidinol was obtained from trans-4- hydroxy-L-proline via decarboxylation, benzylation, Mitsunobu reaction and hydrolysis. Then the two intermediates were subjected to a condensation to afford the title product with an overall yield of 10%, a purity of 99.3 % and ee value of 99.45 %.