Synthesis of Ethyl 7-Chloro-2-oxoheptylate

Ethyl 7-chloro-2-oxoheptylate is an intermediate of cilastatin, which was synthesized through four steps: ethyl 2,2-diethoxyacetate was first produced using dichloroacetic acid as raw materials via esterification, giving ethyl 2,2-diethoxyacetate with yield of 55.6%, then it cyclized with 1,3-propanedithiol to give ethyl 1,3-dithiane-2-carboxylate with yield of 72.4%, the title product was prepared by oxidation of the obtained product derived from alkylation of 1,3-dithiane-2-carboxylate with 1-bromo-5-chloro-pentane with yield of 80%. The improvement of this process simplifying the synthesis of ethyl 2,2-diethoxyacetate and replacing the 1,5-dibromopentane with 1-bromo-5-chloro-pentane reducing the side reactions in dialkylating process made a higher total yield of final product.