| 摘要 |
An improved manufacturing method of a meropenem is provided to have a simple manufacturing process and to be applied to easily by shortening the manufacturing process. An improved manufacturing method of a meropenem comprises steps of: i) manufacturing a compound indicated to a chemical formula 3 in which a carboxylic acid group is activated by reacting a compound indicated as a chemical formula 2 with 1,1-carbonyldiimidazole, wherein, in the formulae, TBS is a t-butyldimethylsilyl group; ii) manufacturing a compound indicated to a chemical formula 5 by reformatsky-reacting a compound indicated as a chemical formula 3 and a bromoacetate derivative indicated as a chemical formula 4, wherein, in the formula, R1 is alkyl group, phenyl radical, benzyl radical, P- nitrobenzyl group of C1~C8; iii) manufacturing diazo compound indicated to a chemical formula 6 by reacting a compound indicated as a chemical formula 5 with azide compound, wherein, in the formula, R2 is hydrogen or alkylsilyl group of C1~C13; iv) manufacturing a compound indicated to a chemical formula 7 by cyclizing a compound indicated as a chemical formula 6; v) manufacturing a compound indicated to a chemical formula 10 by reacting a compound indicated as a chemical formula 7 with diphenyl chlorophosphate and alkylating with a compound indicated as a chemical formula 9 after activating a ketone group and converting it into a phosphate compound, wherein, in the formula, PNB is a p- nitrobenzyl group; and vi) manufacturing the meropenem indicated to a chemical formula 1 by hydrogenating a compound indicated as a chemical formula 10.
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