Hyun-Kuk Noh, J. S. Lee, Yeong-Dae Kim
Sep 3, 2004
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Influential Citations
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Journal
Organic Process Research & Development
Abstract
A novel synthetic route was devised for 4-aminomethyl-3-Z-methoxyiminopyrrolidine methanesulfonate (AMPM), the key intermediate of gemifloxacin, based on chemoselective hydrogenation of the cyano group in 4-cyano-3-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine (CMBP) with minimum reduction of the methyloxime group employing (t-Boc)2O (BOC) as in situ protecting agent. Over Raney nickel or cobalt catalysts, without in situ BOC protection of amine, the side reaction to 4-aminomethyl-3-amino-1-(N-tert-butoxycarbonyl)pyrrolidine (AABP) was extensive by simultaneous hydrogenation of the methyloxime and cyano groups in CMBP, resulting in over-reduction of the desired intermediate, 4-aminomethyl-3-Z-methoxyimino 1-(N-tert-butoxycarbonyl)pyrrolidine (Z-AMBP) all the way to AABP. When in situ BOC protection was performed, the selectivity to the desired 4-(N-tert-butoxycarbonyl)aminomethyl-3-Z-methoxyimino-1-(N-tert-butoxycarbonyl)pyrrolidine (Z-BAMBP) rose to as high as 91% over Raney cobalt by suppressing the...