Trifluoroacetic acid → 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid

Participants

Reaction Steps

Trifluoroacetic acid (18.3 ml) was added to a suspension of benzhydryl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylate (syn isomer) (cis-trans mixture) (16.4 g) and anisole (10.7 ml) in dichloromethane (65 ml) at ambient temperature and stirred for 1.5 hours at the same temperature. To the reaction mixture was added diisopropyl ether (300 ml) under stirring. The resulting precipitate was collected by filtration and washed with diisopropyl ether. The precipitate was added to a mixture of ethyl acetate (100 ml) and water (300 ml) and the mixture was adjusted to pH 8 with 20% potassium carbonate. The separated aqueous layer was adjusted to pH 3.5 with 10% hydrochloric acid under ice-cooling. The precipitate, whose main component was the disired trans isomer, was filtered off and added to water (300 ml). The solution was adjusted to pH 7.5 with saturated aqueous sodium bicarbonate. After removal of the insoluble substance by filtration, the filterate was adjusted to pH 3.5 with 2N-hydrochloric acid under ice-cooling. The precipitate was filtered, washed with ice-cooled water and dried over phosphorus pentoxide in vacuo to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid (syn isomer) (trans isomer) (5.2 g). The filtrate and the washings were combined and the resultant solution was subjected to column chromatography on macroporous non-ionic adsorption resin "Diaion HP-20" and eluted with 30% aqueous solution of isopropyl alcohol. The fraction containing the object compound was concentrated and lyophilized to give 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-ethoxyiminoacetamido]-3-[2-(3-pyridyl)vinyl]-3-cephem-4-carboxylic acid (syn isomer) (cis isomer) (3.7 g).

Provenance & Evidence