Diphenyl chlorophosphate → 4-Nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-1-(4-nitro-benzyloxycarbonyl)pyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Participants

Reaction Steps

91 μl of diphenyl phosphorochloridate and 77 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 152 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 2.0 ml of anhydrous acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, 176 μl of diisopropylethylamine and a solution of 318 mg of (2S,4S)-2-[4-(2-carbamoyloxyethyl)-1-piperazinylcarbonyl]-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine trifluoromethanesulfonate [prepared as described in step (1) above] in 2.0 ml of anhydrous acetonitrile were then added dropwise to the mixture, whilst ice-cooling, and the mixture was stirred at the same temperature for 2 hours. At the end of this time, the reaction mixture was allowed to stand overnight in a refrigerator, after which it was freed from the solvent by distillation under reduced pressure. The resulting residue was mixed with an aqueous solution of sodium hydrogencarbonate and then extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by chromatography through a Lobar column (a product of Merk & Co., Inc., LiChroprep Si60, size B). Those fractions eluted with a 5:1 by volume mixture of ethyl acetate and methanol were collected and concentrated by evaporation under reduced pressure, to give 99 mg of the title compound as a powder.

Provenance & Evidence