布南色林的合成

Synthesis of Blonanserin

以对氟苯甲酸甲酯为起始原料,经取代、水解及环化反应制得4-(4-氟苯基)-5,6,7,8,9,10-六氢环辛烷并[b]吡啶-2(1H)-酮,再经"一锅法"先与三氟甲磺酸酐反应形成活性酯,再经碘代反应得4-(4-氟苯基)-2-碘-5,6,7,8,9,10-六氢环辛烷并[b]吡啶,最后与N-乙基哌嗪在碘化亚铜和碳酸铯的作用下发生亲核取代反应制得布南色林,总收率46%。

The key intermediate 4-（4-fluorophenyl）-5,6,7,8,9,10-hexahydrocycloocta[b]pyridin-2（1H）-one was prepared via substitution, hydrolysis, and cyclization, started from methyl 4-fluorobenzoate. Then it reacted with trifluoromethanesulfonic anhydride to give the active ester, followed by iodination to afford 4-（4-fluorophenyl）-2-iodo- 5,6,7,8,9,10-hexahydrocycloocta[b]pyridine by “one-pot” method. The latter reacted with N-ethyl piperazine in the presence of copper iodide and cesium carbonate to give blonanserin with an overall yield of 46%.