Precise Preparation of a High-Purity Key Intermediate of Tazobactam

In situ IR was used to precisely prepare high-purity diphenylmethyl 6α-bromopenicillanate 8, a key intermediate of tazobactam. 8was obtained when 6α-bromopenicillanic acid 2reacted with diphenyldiazomethane (DDM). 2is 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 8involved 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.