Diphenylphosphinic chloride → (5R,6S)-2-[2-(4-Hydroxyiminopiperidin-1-yl)-2-iminoethylthio]-6-[(1R)-1-hydroxyethyl]-1-carbapen-2-em-3-carboxylic acid

Participants

Reaction Steps

0.21 ml of diisopropylethylamine and 0.22 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 363 mg of p-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 5 ml of anhydrous acetonitrile, and the mixture was stirred for one hour with ice-cooling. A solution of 0.18 ml of diisopropylethylamine and 324 mg of 2-(4-hydroxyiminopiperidin-1-yl)-2-iminoethylmercaptan hydrochloride in 3 ml of dimethylsulfoxide was then added dropwise to the mixture, which was stirred for a further 20 minutes with ice-cooling. The reaction mixture was then poured into 100 ml of anhydrous ether, and the solvent was decanted off from the gummy material which formed. This material was dissolved in a mixture of 20 ml of tetrahydrofuran, 7 ml of water and 23 ml of 0.1M phosphate buffer (pH 7.0), and the solution was subjected to catalytic hydrogenation at room temperature for 4 hours in the presence of 0.3 g of 10% palladium-carbon. The hydrogenated solution was filtered over "Celite" (Trade Mark) filter aid, the filtrate was extracted with 200 ml of ether, and the aqueous layer was concentrated under reduced pressure. The concentrate was subjected to chromatography using a 300 ml column of "Dowex 50W" (Trade Mark) cation exchange resin (Na+ type), and 27 mg of the title compound were obtained from the fraction eluted with water.

Provenance & Evidence