Oxalyl chloride → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(3S)-2-oxopyrrolidin-3-yl]oxyiminoacetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Steps

1.81 g of oxalyl chloride are added at 5° to 0° C. to 45 ml of chloroform containing 1.15 ml of dimethylformamide, and the mixture is stirred at the same temperature for 15 minutes. A solution of 4.90 g of (Z)-2-(2-tritylaminothiazol-4-yl)-2-[((3S)-2-pyrrolidon-3-yl)oxyimino]acetic acid and 0.97 g of triethylamine in 45 ml of chloroform is added to said mixture at -30° C. The mixture is stirred at the same temperature for 5 minutes. Then, a solution of (6R, 7R)-7-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate in chloroform (said solution is prepared by suspending 5.8 g of the dihydrochloride of said cephem compound in 45 ml of chloroform and adding 12.7 ml of N,O-bis(trimethylsilyl)acetamide thereto to dissolve said salt therein) is added to the mixture at -30° to -10° C. After the mixture is stirred at the same temperature for 30 minutes, said mixture is concentrated to dryness under reduced pressure. 100 ml of 80% aqueous formic acid are added to the residue, and the aqueous mixture is stirred at room temperature for one hours. 110 ml of water are added to the mixture, and insoluble materials are filtered off. The filtrate is washed with ethyl acetate and is concentrated to dryness under reduced pressure. The residue thus obtained is dissolved in water and chromatographed on a column of non-ionic polymer resin Diaion HP-20 (resistered trade mark, manufactured by Mitsubish Chemical Industries Ltd., Japan). The column is washed with water, followed by elution with 20% aqueous methanol. The franctions containing the cephalosporin compound are collected and concentrated to dryness under reduced pressure. Acetone is added to the residue, and the resulting powder is collected by filtration. 2.22 g of (6R, 7R)-7-{(Z)-2-(2-aminothiazol-4-yl)-2-[((3S)-2-pyrrolidon-3-yl)oxyimino]acetamido}-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate are obtained.

Provenance & Evidence