Abstract
A short and simple synthesis of 2β-(1,2,3-Triazol-1-yl) methyl-2α-methyl-6,6-dihydropenicillin-3α-carboxylic acid diphenylmethyl ester (7), on multi-gram scale, is described. Compound 7 is the key intermediate for the synthesis of tazobactam. Mercury (II) acetate and azobisisobutyronitrile (AIBN) were used to optimize the direct substitution of 1,2,3-triazole (to avoid hazardous sodium azide and extremely flammable/asphyxiant acetylene gas) to the commercially available starting material benzhydryl 2-((R)-2-(2-(benzo[d]thiazol-2-yl)disulfanyl)-4-oxoaze. Efficient recovery of 1,2,3-triazole was attained. A plausible mechanism for synthesis of 7 is presented. The target tazobactam was obtained with 99.69% purity by HPLC without column chromatographic purification, and with 49% overall yield from 7 as the starting material.
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Acknowledgements
We gratefully acknowledge Ram Prasad Yadav, Mohammad Rafeeq for their technical suggestions and Ravindra Yeole for analytical support. We extend our gratitude to Bharat Kashid and chemical research laboratory members for providing useful feedback.
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Tamboli, Y., Pund, A.P., Kilbile, J.T. et al. Hg(OAc)2/1,2,3-triazole-mediated efficient synthesis of Tazobactam. Chem. Pap. 77, 1247–1251 (2023). https://doi.org/10.1007/s11696-022-02545-x
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DOI: https://doi.org/10.1007/s11696-022-02545-x