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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。
The chiral resolution of the title compound was studied and optimized to obtain its single S-type isomer. Diastereomers were formed with the title compound using (S) -4-nitro-1-phenylethylamine hydrochloride as a chiral resolving agent, and chiral resolution was performed using the difference in solubility between the two to give The intermediate (S) -2-hydroxy-3-methoxy-3,3-diphenylpropionic acid (S) -4-nitro- -2-hydroxy-3-methoxy-3,3-diphenylpropionic acid. The amount of solvent, the amount of resolving agent, the amount of acid-binding agent and the conditions of recrystallization were investigated. At the same time, the chiral resolving agent was recovered. The results showed that 100 g of the title compound as the starting material, 20 times the volume of absolute ethanol as the solvent, the amount of 1.5 times the amount of triethylamine acid-binding agent and the use of 0.75 times the amount of the resolving agent , Good yield (40.6%) and optical purity (82.8% ee) were obtained, which were further recrystallized to meet the quality requirements (ee> 99.00%). The process has the advantages of simple operation, low cost and high quality, suitable for industrialized production.