克唑替尼关键中间体(S)-1-(2,6-二氯-3-氟苯基)乙醇的不对称合成

(S)-1-(2,6-二氯-3-氟苯基)乙醇（2）是合成抗癌药物克唑替尼的关键手性前体。本文以1-(2,6-二氯-3-氟苯基)乙酮为起始原料，利用二异松莰基氯化硼［(-)-Ipc₂BCl］不对称还原制得光学纯的2；并将中间体2经Mitsunobu反应、还原、溴代、 Suzuki偶联及脱除Boc保护合成克唑替尼，其结构¹H NMR，¹³C NMR和HR-MS(ESI)确证。对关键中间体2的合成条件进行了优化，并其对反应机理进行了推测。

Synthesis of Crizotinib Key Intermediate ( S)-1-(2,6-Dichloro-3-fluorophenyl) ethanol

Using (-)-Ipc2 BCl as the chair reduction agent , corresponding chiral precursor of Crizo-tinib.(S)-1-(2,6-dichloro-3-fluorophenyl) ethanol (2) was yielded by asymmetric reduction from 2, 6-dichloro-3-fluro acetophenone .Based on key intermediate 2 , Crizotinib was synthesized .The process included Mitsunobu reaction , reduction of an arylnitro group , bromination reaction , Suzuki coupling and Boc deprotection .The structure of target compound was confirmed by 1 H NMR, 13 C NMR and HR-MS( ESI ) .The synthetic process of key intermediate 2 was optimized and the possible reaction mechanism was proposed .