依非韦伦中间体的不对称合成

为了优化依非韦伦手性中间体（S）-1-（2-氨基-5-氯苯基）-1-三氟甲基-3-环丙基-2-丙炔-1-醇的不对称合成工艺。以对氯苯胺为起始原料，经过氨基保护、酰化反应、氨基脱保护、碱化、不对称加成得到目标化合物。所得化合物结构均经核磁共振氢谱和碳谱确证。得到不对称加成反应最佳工艺条件:2-甲基四氢呋喃/甲苯为溶剂，4-氯-2-（三氟乙酰基）苯胺的浓度为0.45 mol/L，4-氯-2-（三氟乙酰基）苯胺、（1R， 2S）-1-苯基-2-（吡咯烷基）-1-丙醇与ZnCl2的摩尔比为1.0∶1.2∶1.3，总收率达79.8%（以对氯苯胺计），对映体过量98.2%。优化后的工艺条件具有成本低、收率高，适合工业生产的特点。

Asymmetric Synthesis of Efavirenz Intermediates

To improve the asymmetric synthesis process of chiral intermediate（S）-1-（2-amino- 5-chlorophenyl）-1-trifluoromethyl-3-cyclopropyl-2-propyne-1-ol of efavirenz，we prepared the target compound via amino protection， acylation reaction， deprotection， alkalinization and asymmetric addition reaction with p-chloroaniline as the raw material. The chemical structure of compounds was confirmed by 1H and 13C nuclear magnetic resonance spectroscopy. The optimum process conditions of asymmetric addition reactions were determined using 2-MeTHF/toluene as solvent， at 0.45 mol/L of 4-chloro-2-（trifluoro acetyl）， mole ratio of 4-chloro-2-（trifluoro acetyl） aniline/（1R， 2S）-1-phenyl-2-（pyrrolidinyl）-1-propanol/Zinc chloride of 1.0∶1.2∶1.3. Under above conditions， the total yield reaches 79.8% （calculated by p-chloroaniline） and the enantiomeric excess is 98.2%. The improved process has the characteristics of lower cost， higher yield， which is suitable for industrial production.