Synthesis of key intermediates of β-lactamase inhibitors by microchannel technology
Microchannel technology was used to improve the synthesis efficiency of(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid(Ⅰ),a key intermediate of novel β-lactamase inhibitors based on diazabicyclooctane(DBO).Through the investigation of solvent,temperature,residence time and base,the process conditions were optimized.The results show that the hydrolysis of(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid benzyl ester(Ⅱ)in microchannel reactor is best conducted with acetone as a solvent and lithium hydroxide as a base at 45℃for 20 min.The product was identified by 1H nuclear magnetic resonance spectroscopy,13C nuclear magnetic resonance spectroscopy and high resolution mass spectroscopy.The key intermediate(Ⅰ)is obtained in 95％yield.Thus this technology significantly increases the rate and yield of this reaction and makes it feasible to industrial production.
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