ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Hg(OAc)₂/1,2,3-triazole-mediated efficient synthesis of Tazobactam

Yasinalli Tamboli, Amit P. Pund, Jaydeo T. Kilbile, and Arvind Y. Merwade

Wockhardt Research Centre, Aurangabad, India

E-mail: yasinmedchem@gmail.com

Received: 8 July 2022  Accepted: 12 October 2022

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.

Graphical abstract

Keywords: Tazobactam; β-lactamase inhibitor; 1,2,3 triazole; Mercury (II) acetate

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02545-x

Chemical Papers 77 (2) 1247–1251 (2023)