4-Nitrobenzyl (1R,5S,6S)-2-((2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio)-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate → (1R,5S,6S)-2-[(2S,4S)-2-(3-Aminoazetidin-1-ylcarbonyl)pyrrolidin-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylic acid

Participants

Reaction Steps

3630 mg of 4-nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate [prepared as described in Example 121(1)] were dissolved in 190 ml of a 3:2 by volume mixture of tetrahydrofuran and water, and 5500 mg of a 10% w/w palladium-on-carbon catalyst were added to the resulting solution. The mixture was then hydrogenated at 30° C. for 1.5 hours in an atmosphere of hydrogen. At the end of this time, the catalyst was removed by filtration, the filtrate was washed with diethyl ether and the resulting aqueous solution was concentrated to 10 ml by evaporation under reduced pressure. The resulting solution was subjected to reverse phase silica gel column chromatography (Cosmosil 75C18 -prep, 250 ml, manufactured by Nacalai Tesque), eluted with mixtures of acetonitrile and water in proportions of 0:100, 2:98, 4:96, 6:94 by volume, in that order. The fractions containing the title compound were collected, concentrated by evaporation under reduced pressure and freeze-dried, to obtain 901 mg of the title compound as a powder.

Provenance & Evidence