Diphenylphosphinic chloride → (5R, 6S)-2-[(3S)-1,1-Dimethylpyrrolidinium-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylate

Participants

Reaction Steps

183 μl of diisopropylethylamine and 218 μl of diphenylphosphoryl chloride were simultaneously added, whilst ice-cooling, to a solution of 348 mg of 4-nitrobenzyl (5R, 6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate dissolved in 4 ml of dry acetonitrile and the mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 338 mg of the crude (3S)-1,1-dimethyl-3-mercaptopyrrolidinium salt prepared as described in Example 5-(1) in 4 ml of dry acetonitrile and 209 μl of diisopropylethylamine were added to the mixture, whilst ice-cooling. The mixture was then allowed to stand at the same temperature for 1 hour and then for two days in a refrigerator. At the end of this time, the reaction mixture was washed by decantation with diethyl ether. The resulting product was dissolved in a mixture of 30 ml of tetrahydrofuran and 30 ml of a 0.1M phosphate buffer (pH 7.0) and hydrogenated at room temperature for 2.5 hours in the presence of 400 mg of 10% w/w palladium-on-charcoal. At the end of this time, an insoluble material was removed by filtration and the filtrate was washed with diethyl ether. The aqueous layer was concentrated by evaporation under reduced pressure and then subjected to column chromatography through Diaion HP-20AG (Mitsubishi Chemical Industries, Inc.). The title compound was prepared as a crude product from the fractions eluted with water. The crude compound was then further purified by chromatography through a Lobar column (Merck Co. LiChroprep RP-8, size B) and the fractions eluted with 5% by volume aqueous methanol were collected, concentrated by evaporation under reduced pressure and lyophilized to afford 60 mg of the title compound.

Provenance & Evidence