Sodium Iodide → HCID 178508508, compound

Participants

Reaction Steps

To the solution of 0.25 g (0.3 mole) of p-methoxybenzyl (6R,7R)-7-[(Z)-2-(5-tritylamino-1,2,4-thiadiazol-3-yl)-2- fluoroethoxyiminoacetamido]-3-chloromethyl-3-cephem-4-carboxylate in 5 ml of acetone was added 0.17 g (1.4m mole) of sodium iodide, and the mixture was stirred in darkness at room temperature for 1 hour. After the acetone was removed under reduced pressure, the residue was dissolved in ethyl acetate and washed with a small amount of a saturated aqueous solution of sodium thiosulfate, and then saturated saline. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was dissolved in 3 ml of DMF. A solution of 0.07 g of 5-[(R)-1-(formylamino)-2-hydroxyethyl]imidazo[5,1-b]thiazole (Preparation 58) in 1 ml of DMF was added to the above solution, and the mixture was stirred in darkness at room temperature overnight. To the reaction mixture was added 20 ml of a 10% aqueous sodium trifluoroacetate solution, and the resulting sediments were collected by centrifugation, washed twice with a 10% aqueous sodium trifluoroacetate solution and dried in vacuum for 1 hour. To the residue thus obtained were added under ice-cooling 1 ml of anisole and 3 ml of trifluoroacetic acid, and the mixture was stirred for 1 hour. Twenty milliliter of isopropyl ether was added to the reaction mixture, and the resulting solids were sedimented by centrifugation. The precipitate were washed with isopropyl ether and then dried in vacuum. A 5% aqueous sodium hydrogen carbonate solution was added to the product to neutralize and dissolve it. The resulting solution was purified by column chromatography on Diaion HP-20 resin (eluent: 200 ml of water, 50 ml of 5% methanol-water, 50 ml of 10% methanol-water, 100 ml of 15% methanol-water, 100 ml of 20% methanol-water, 100 ml of 25% methanol-water, 100 ml of 30% methanol-water, 100 ml of 40% methanol-water). The fraction containing the aimed product was concentrated and lyophilized to give 0.016 g of the title compound. Yield 8%. NMR (D2O) δ: 3.15 (1H, d, J=17 Hz), 3.41 (1H, d, J=17 Hz), 3.97-4.06 (2H, m), 4.40-4.51 (1H, m), 4.58-4.68 (1H, m), 5.15 (1H, d, J=5 Hz), 5.34 (2H, brs), 5.59-5.61 (1H, m), 5.78 (1H, d, J=4 Hz), 7.48 (1H, d, J=4 Hz), 7.66 (1H, s), 7.91-7.94 (1H, m), 8.05 (1H, s).

Provenance & Evidence