The invention is a process improvement for producing the carbapenem antibacterial agent (4R, 5S, 6S)-3-[[(2R, 3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid by hydrogenation of 4-nitrobenzyl (4R, 5S, 6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-{[(2R, 3R)-2-({[(2S)-3-methyl-2-({[(4-nitrobenzyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-tetrahydrofuran-3-yl]thio}-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in a biphasic solvent mixture comprising a water portion and an organic solvent portion, not containing an acid acceptor. Separating the water portion from the organic portion and isolating (4R, 5S, 6S)-3-[[(2R, 3R)-2-[[[(S)-2-amino-3-methyl-1-oxobutyl]amino]methyl]tetrahydro-3-furanyl]thio]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid from the separated water portion by lyophilization or reverse osmosis.
这项发明是一种用于生产碳青霉烯抗菌剂(4R, 5S, 6S)-3-[[[(2R, 3R)-2-[[[(S)-2-
氨基-3-甲基-1-氧丁基]
氨基]甲基]四氢-3-
呋喃基]
硫]-6-[(R)-1-羟乙基]-4-甲基-7-羟基-1-
氮杂双环[3.2.0]庚-2-烯-2-
羧酸的工艺改进,通过在由含有
水部分和有机溶剂部分组成的两相溶剂混合物中氢化4-硝基苄(4R, 5S, 6S)-6-[(1R)-1-羟乙基]-4-甲基-3-[(2R, 3R)-2-([(2S)-3-甲基-2-([4-硝基苄]氧}羰基)
氨基]丁酰
氨基}甲基)-
四氢呋喃-3-基
硫}-7-氧基-1-
氮杂双环[3.2.0]庚-2-烯-2-
羧酸。将
水部分与有机部分分离,并通过冻干或反渗透从分离的
水部分中分离出(4R, 5S, 6S)-3-[[[(2R, 3R)-2-[[[(S)-2-
氨基-3-甲基-1-氧丁基]
氨基]甲基]四氢-3-
呋喃基]
硫]-6-[(R)-1-羟乙基]-4-甲基-7-羟基-1-
氮杂双环[3.2.0]庚-2-烯-2-
羧酸。