Diphenylphosphinic chloride → 4-Nitrobenzyl (1R,5S,6S)-2-{(2S,4S)-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-methylpyrrolidin-4-ylthio}-6-[(1R)-1-hydroxyethyl]-1-methyl-1-carbapen-2-em-3-carboxylate

Participants

Reaction Steps

600 μl of diphenylphosphoryl chloride and 510 μl of diisopropylethylamine were added dropwise, whilst ice-cooling, to a solution of 1000 mg of 4-nitrobenzyl (1R,5S,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 10 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. 1800 μl of diisopropylethyl-amine and a solution of 1680 mg of (2S,4S)-4-mercapto-2-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-1-methyl-pyrrolidine bis(trifluoromethanesulfonate) (prepared as described in Preparation 52) in 5 ml of dry acetonitrile were then simultaneously added dropwise to the mixture, whilst ice-cooling, and the resulting mixture was stirred at the same temperature for 2 hours, after which it was allowed to stand overnight in a refrigerator. At the end of this time, the solvent was removed by distillation under reduced pressure, and the residue was subjected to column chromatography through a Lobar column (Merck, LiChroprep RP-8, size B). The column was eluted first with 55% v/v aqueous methanol and then with 60% v/v aqueous methanol. Those fractions containing the title compound were collected, concentrated by evaporation under reduced pressure and lyophilized, to give 710 mg of the title compound, as a powder.

Provenance & Evidence