The Synthesis Of4-acetoxyazetidin-2-one

(3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)-ethyl]-2-azetidinone, named4AA for short, molecular formula C13H25NO4S1, molecular weight287.43, melt point104～108℃.4AA is an important intermediate to synthesis carbapanems which belongs to β-lactam antibiotics. Since the Sankyo Ltd. Co. published the first method of4AA synthesis, more and more companies and colleges has to study this intermediate. There has no less than twenties reports has been published. This paper made a lot of pains to optimize the reaction conditions in order to find a more reasonable method of the4AA synthesis.This paper chooses two methods to synthesize4AA after summarize published methods. One route is using6-aminopenicillanic acid as the starting material, the target molecule4-acetoxyazetidin-2-one was synthesized through bromination, esterification, Grignard reaction, reduction, protection, ring-opening and oxidation. The structure was verified by1HNMR. Some reaction conditions were optimized. The total yield reached27.9%. In the program, the most important step undergoes by low temperature, and got several stereoisomers after reaction which is difficult used on industrial produce. This paper compares the other method which used asymmetry catalyst to synthesize4AA. The other route is using benzamide as the starting material, the target molecule4-acetoxyazetidin-2-one was synthesized through asymmetry catalysis, hydrolyze, loop and oxidation. The structure was verified by1HNMR. Some reaction conditions were optimized. The total yield reached29.6%.