Studies On The Synthesis Of The Key Intermediate Of ICE Inhibitor

4-bromo-5-ethoxy-2(5H)-furanone as a key intermediate of ICE inhibitor, its industrial production has been attentioned by various pharmaceutical companies and chemical companies in the world.A novel synthetic method has been designed in the synthesis of 4-bromo-5-ethoxy-2(5H-furanone according to many references. The synthesis started from commercially available furfural and carried out in 4 steps, including Baeyer-Villiger oxidation, bromination, Williamson etherification, and bromination once again.In the oxidation reaction, changing the way of feeding the start materials, the process of the reaction was controlled very well and the risk of explosion was reduced, the yield of such reaction has been raised by 10-20%. In order to improve the selectivity and yield of the bromination reaction, some hydroxy-protecting group is introduced to such reaction, and the reaction was done in one-pot, a lot of time has been saved and lead to high yield of 85%; the final step-bromination reaction:the intermediate was addition with bromine, then the pre-product was transited to the final product by way of heating in high vacue to eliminate HBr, this method was firstly uesd in the synthesis of the compound.The novel method for the synthesis of 4-bromo-5-ethoxy-2(5H)-furanone contain such highlights:good yield, simple operation, the entire process is relatively friendly to the environment and suitable for industrial production.