INTERMEDIATE OF CILASTATIN AND PREPARATION METHOD THEREOF

摘要

Disclosed is a method for preparing 7-halo-2-oxoheptylate, an intermediate of cilastatin. The main steps are as follows: A. Addition reaction, in which 6-halo-hexanal is reacted with a cyanide to obtain 7-halo-±-hydroxyl-heptonitrile; B. Hydrolysis reaction, in which 7-halo-±-hydroxyl-heptonitrile is converted to 7-halo-±-hydroxyl-heptylic acid; C. Esterification reaction, in which 7-halo-±-hydroxyl-heptylic acid is converted to 7-halo-±-hydroxyl-heptylate; and D. Oxidation reaction, in which 7-halo-±-hydroxyl-heptylate is converted to 7-halo-2-oxoheptylate. 7-halo-±-hydroxyl-heptylic acid or ester thereof, which is a new intermediate for synthesizing 7-halo-2-oxoheptylate or cilastatin, and a method for synthesizing cilastatin are also disclosed. The methods of the invention are suitable for commercial production because of their simple process and mild reaction condition.