Precise Preparation of a High-Purity Key Intermediate of Tazobactam,Organic Process Research & Development

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Precise Preparation of a High-Purity Key Intermediate of Tazobactam
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-11-23 , DOI: 10.1021/acs.oprd.0c00407
Yanan Zhou ₁ , Chengjun Wu ₁ , Hongzhi Ma ₁ , Jianchao Chen ₁ , Tiemin Sun ₁

Affiliation

In situ IR was used to precisely prepare high-purity diphenylmethyl 6α-bromopenicillanate 8, a key intermediate of tazobactam. 8 was obtained when 6α-bromopenicillanic acid 2 reacted with diphenyldiazomethane (DDM). 2 is unstable and must therefore react immediately with DDM upon preparation. DDM is also unstable. As DDM decomposes rapidly upon preparation, the DDM content cannot be precisely determined using high-performance liquid chromatography (HPLC) or gas chromatography (GC). Therefore, good yield and purity are difficult to obtain, resulting in large batch-to-batch variations (yield 69.3–82.8%, purity 89.8–98.4%) for 8. The developed preparation method for 8 involved the use of in situ IR to monitor the reaction process and achieved good results (82.7–83.1% yield and 97.3–98.5% purity). This method was also used to prepare the key intermediate for the synthesis of cephalosporin derivatives, which have high industrial value.

中文翻译：

他唑巴坦的高纯度关键中间体的精确制备

原位红外光谱法用于精确制备高纯度的二苯甲基6α-溴Openicillanate 8，这是他唑巴坦的关键中间体。当6α-溴Openicillanic酸2与二苯基重氮甲烷（DDM）反应时，获得8。2是不稳定的，因此在制备时必须立即与DDM反应。DDM也是不稳定的。由于DDM在制备时会迅速分解，因此无法使用高效液相色谱（HPLC）或气相色谱（GC）精确测定DDM含量。因此，良好的产率和纯度是很难获得的，从而为大批与批料变化（收率69.3-82.8％，纯度89.8-98.4％）8。已开发的8种制备方法涉及使用原位红外监测反应过程并获得了良好的结果（产率为82.7-83.1％，纯度为97.3-98.5％）。该方法还用于制备合成头孢菌素衍生物的关键中间体，具有很高的工业价值。

更新日期：2020-12-18

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