(4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[(3S,5S)-1-methyl-5-[4-[N-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]piperazine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate → (1R,5S,6S)-2-[(2S,4S)-2-(4-Amidinopiperazin-1-ylcarbonyl)-1-methylpyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

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Reaction Steps

500 ml of 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-{(2S,4S) -1-methyl-2-[4-(4-nitrobenzyloxycarbonylamidino)piperazin-1-ylcarbonyl]-pyrrolidin-4-yl-thio}-1-carbapen-2-em-3-carboxylate [prepared as described in step (1) above] were dissolved in 75 ml of a 1:1 by volume mixture of tetrahydrofuran and water, and 2400 mg of a 10% w/w palladium-on-carbon catalyst were added to the resulting solution. The mixture was then hydrogenated in an atmosphere of hydrogen at 28° C. for 1 hour. At the end of this time, the catalyst was removed by filtration, and the filtrate was washed with diethyl ether. The filtrate was then concentrated to 20 ml by evaporation under reduced pressure. The solution was then subjected to reverse phase silica gel column chromatography (Cosmosil 75C18 -prep, manufactured by Nacalai Tesque, 100 ml), eluted with mixtures of acetonitrile and water in proportions of 0:100, 2:98, 4:96, 6:94 and 8:92 by volume, in that order. The fractions containing the desired compound were collected, concentrated to 3 ml by evaporation under reduced pressure, and cooled to precipitate colorless needle-like crystals. The crystals were filtered off and dried to obtain 435 mg of the title compound as crystals, melting at 218°-220° C. (with decomposition).

Provenance & Evidence