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