Ethyl 7-chloro-2-oxoheptanoate is an important intermidiate of cilastatin. Using macronano-K2CO3 as base, 2-(5-chloropentyl)malonate was synthesized from 1-bromo-5-chloropentane and diethyl malonate in anhydrous EtOH, and then it was oxided by air catalized by Cu(NO3)2.3H2O in CH3CN to give ethyl 7-chloro-2-oxoheptanoate. The influence factors of the first-step reaction and the second-step reaction were investigated. The optimaized overall yield was 90.2%. The target product was characterized by means of 1HNMR and 13CNMR.