米铂的合成工艺改进

Improved Synthetic Process of Miriplatin

本研究对米铂(1)的合成工艺进行了改进。十四烷酸(2)和氢氧化钠在乙酸乙酯/纯化水混合溶剂中反应,经静置析晶得十四烷酸钠(3)。3和奥沙利铂(4)在水中反应,经静置析晶、抽滤、热纯化水淋洗和精制后得1,纯度达99.91%,总收率79%(以2计),并且将1中3和草酸的含量均降至0.05%以下。优化后的工艺对原料2的质量要求降低:同系物十至十六烷酸单杂含量不超过0.2%,各杂质含量之和不超过1.0%即可得到合格产品,后处理简单,易于工业化生产。

The synthetic process of miriplatin(1)was improved.Tetradecanoic acid(2)reacted with NaOH in ethyl acetate/pure water and purified by static crystallization to give sodium tetradecanoate(3).Compound 3 reacted with oxaliplatin(4)in water to give crude 1,which was followed by standing for crystallization,suction filtration,hot pure water washing and refining to obtain the final product in a purity of 99.91%and a total yield of 79%(based on 2).The contents of both 3 and oxalic acid in 1 were less than 0.05%.The quality requirements for raw material 2 in this process for synthesis of the qualified product were decreased:the content of any individual impurity in the homologous(C10-C16 acids)was no more than 0.2%,and the total impurities were no more than 1.0%.The work-up was simple,and this process was more feasible for industrial production.