Phosphorus oxychloride → Sodium 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylate

Participants

Reaction Steps

A solution of 7-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid (2.5 g.) and trimethylsilylacetamide (10.6 g.) in dry ethyl acetate (60 ml.) and a mixture of dimethylformamide (0.75 ml.), phosphoryl chloride (0.88 ml.), 2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer, 2.5 g.) and dry ethyl acetate (7.0 ml.) were stirred at -20° to -10° C. for an hour. The reaction mixture was added to aqueous solution (50 ml.) of sodium bicarbonate (3.3 g.), under ice-cooling. Methanol (2 ml.) was added to the mixture and stirred under ice-cooling for 30 minutes. The mixture was washed with ethyl acetate twice. After removing the ethyl acetate, the aqueous solution was adjusted to pH 6.5 with sodium bicarbonate and allowed to stand in a refrigerator. The solution was adjusted to pH 5.0 with 6N-hydrochloric acid and subjected to column chromatography on non-ionic adsorption resin HP-20 (Trademark, manufactured by Mitsubishi Chemical Industries Ltd.), washed with water (200 ml.) and then eluted with 20% isopropyl alcohol (400 ml.). The eluate was evaporated in vacuo. The residue was pulverized with acetone (80 ml.), and the precipitates were collected by filtration and dried to give sodium 7-[2-(2-formamido-5-bromothiazol-4-yl)-2-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylate (syn isomer, 1.9 g.).

Provenance & Evidence