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

Participants

Reaction Steps

1.83 ml of diisopropylethylamine and 2.18 ml of diphenylphosphoryl chloride were added dropwise to an ice-cooled solution of 3.48 g of 4-nitrobenzyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate in 20 ml of anhydrous acetonitrile, and the mixture was stirred for one hour with ice-cooling. The reaction mixture was then added to a mixture of 2.1 ml of diisopropylethylamine in 70 ml of tetrahydrofuran and 60 ml of 0.1M phosphate buffer solution (pH 7.0), which had been cooled with ice and salt, together with 10 ml of an aqueous solution of 3.17 g of 2-(4-carbamoyloxypiperidin-1-yl)-2-iminoethylmercaptan hydrochloride, and the resulting mixture was stirred for 5 minutes. The reaction mixture was then subjected to hydrogenation at room temperature for 2 hours, in the presence of 3.0 g of 10% palladium-carbon. The hydrogenated reaction mixture was worked up in the same manner as in Example 1(3), giving 783 mg of the title compound.

Provenance & Evidence