Affiliation:
1. Department of Organic Synthesis and Process Chemistry CSIR-Indian Institute of Chemical Technology Hyderabad 500 007 India
2. Academy of Scientific and Innovative Research (AcSIR) Ghaziabad 201 002 India
Abstract
AbstractA chemo‐enzymatic route for the preparation of (S,S)‐2,8‐diazabicyclo[4.3.0]nonane, a key chiral intermediate of Moxifloxacin, has been evaluated and improved. The activity of immobilized Candida antarctica lipase B was found to be increased four times for the selective hydrolysis of cis‐dimethyl 1‐acetylpiperidine‐2,3‐dicarboxylate at 50 °C as compared to 27 °C. The reaction has an optimum temperature of 50–60 °C and an optimum pH of 7.5. The reaction follows typical Michaelis‐Menten kinetics with Vmax,obsd=2472 units/g, Km,obsd=0.334 M, n=6, correlation coeff. r=0.995 at 50 °C. The reaction time and enzyme loading were reduced to 26 h at 15 % (w/w) as compared to 14 days at 50 % (w/w) loading. The enzyme was found to be recyclable up to 5 times. Further, the reduction of dimethyl pyridine‐2,3‐dicarboxylate was performed at a temperature of 27 °C under an H2‐filled balloon, in the presence of Pd/C and acetic acid, under atmospheric pressure to give cis‐(±)‐Dimethylpiperidine‐2,3‐dicarboxylate. We anticipate that our results will be beneficial to the pharmaceutical industry for the large‐scale production of (S,S)‐2,8‐diazabicyclo[4.3.0]nonane.
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