| 主权项 |
1. An improved process for the preparation of Tazobactam of formula (I) which comprises the steps of:
i) reacting compound of formula (II) wherein R is selected from p-methoxybenzyl, diphenylmethyl(benzhydryl), 3,4,5-tirmethoxybenzyl, 2,4-dimethoxybenzyl, 3,5-dimethoxy-4-hydroxybenzyl, 2,4,6-trimethylbenzyl, ditolylmethyl, dianisylmethyl or tert-butyl with mercaptan of formula R′−SH in the presence of an organic solvent to get compound of formula (III); wherein R has the meaning given above and R′ is selected from benzothiazol-2-yl, benzoxazol-2-yl, benzimidazol-2-yl, 5-methyltetrazol-2-yl,ii) converting the compound of formula (III) to compound of formula (IV) wherein R has the meaning given above and X represents a leaving group selected from the group consisting of chloro, bromo, iodo, mesylate, tosylate, besylate and triflate in the presence or absence of second organic solvent and phase transfer catalyst;iii) converting the compound of formula (IV) to compound of formula (V); wherein R has the meaning given above;iv) oxidizing compound of formula (V) to get compound of formula (VI); wherein R has the meaning given above;v) deprotecting compound of formula (VI) with cresol to get tazobactam of formula (I); andvi) extracting the tazobactam of formula (I) into aqueous layer optionally using base;vii) acidifying the solution to yield Tazobactam of formula (I);wherein the improvement consists of either or both of the following
a) carrying out steps (i) to (iii) in situ and without isolating the intermediates (III) and (IV);b) acidification in step (vii) is carried out in the presence of water-miscible solvent. |
