摘要
研究并优化了标题化合物的手性拆分工艺,获得其单一的S型异构体。以(S)-4-硝基-1-苯乙胺盐酸盐为手性拆分剂,与标题化合物生成非对映异构体,利用两者溶解性差异来进行手性拆分,得到中间体(S)-2-羟基-3-甲氧基-3,3-二苯基丙酸(S)-4-硝基-1-苯乙胺盐,经酸性游离后得到产物(S)-2-羟基-3-甲氧基-3,3-二苯基丙酸。对溶剂量、拆分剂的量、缚酸剂的量以及重结晶条件进行了考察,同时对手性拆分剂进行了回收。结果表明,以100 g标题化合物为起始原料,20倍体积的无水乙醇为溶剂,1.5倍物质的量的三乙胺为缚酸剂并使用0.75倍物质的量的拆分剂进行拆分时,得到了较好的产率(40.6%)和光学纯度(82.8%e.e.),经进一步重结晶达到质量要求(e.e.>99.00%)。该工艺具有操作简便、产品成本低且质量较高的优点,适用于工业化生产。
Research and optimize the chiral resolution of racemic 2-hydroxy-3-methoxy-3,3-diphenyl-propionic acid to obtain its single S-isomer. As a chiral resolving agent,（ S）-1-（ 4-Nitro-phenyl）-ethylamine hydrochloride salifys with 2-hydroxy-3-methoxy-3,3-diphenyl-propionic acid and generates a couple of diastereoisomers,which can be separated by their different solubility in solution. Acidize the diastereoisomer intermediate to obtain the product（ S）-2-hydroxy-3-methoxy-3,3-diphenyl-propionic acid. The amount of solvent,resolving agent,acidscavenger,recrystallization condition and the chiral resolving agent’s reclamation have been investigated. With 100 g racemic 2-hydroxy-3-methoxy-3,3-diphenyl-propionic acid as start material,in the condition of 20 equivalent of ethanol as solvent,1. 5 equivalent of triethylamine as acidscavenger and 0. 75 equivalent of solving agent,the resolution obtains the best yield（ 40. 6%） and optical purity（ 82. 8% e. e.）,which can reachthe quality requirement（ e. e.〉 99. 00%） after further recrystallization. With the advantages of simple in process,low-cost of raw materials and high-quality of product,the chiral resolution is suitable for industrial production.
出处
《化学试剂》
CAS
北大核心
2015年第7期639-642,共4页
Chemical Reagents
