Sodium Chloride → 7-[2-Benzyloxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Participants

Reaction Steps

Phosphorus oxychloride (2.3 g.) was added at a time to a suspension of 2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetic acid (syn isomer) (3.4 g.) in dry tetrahydrofuran (30 ml.) at -3° C. and the mixture was stirred for 20 minutes at the same temperature. Trimethylsilylacetamide (2.4 g.) and tetrahydrofuran (5 ml.) were added dropwise thereto and the resulting mixture was stirred for 20 minutes at the same temperature. Phosphorus oxychloride (2.3 g.) was added thereto and the mixture was stirred for 30 minutes at 0° to 3° C. Dry dimethylformamide (1.1 g.) was added thereto at a time at 0° to 3° C. and the mixture was stirred for 1 hour at the same temperature to give a clear solution. On the other hand, trimethylsilylacetamide (12.7 g.) was added to a stirred suspension of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (4.0 g.) in dry ethyl acetate (60 ml.) and the solution was stirred for 1 hour at ambient temperature. To this stirred solution was added the above-obtained tetrahydrofuran solution at a time at -20° C., and the resulting mixture was stirred for 2 hours at -5° to -15° C. To the reaction mixture were added a saturated aqueous solution of sodium chloride (50 ml.). An organic layer was separated and extracted with a saturated aqueous solution of sodium bicarbonate (pH 7.0). The extract was washed with ethyl acetate, treated with an activated charcoal and adjusted to pH 4.5 with 10% hydrochloric acid. Precipitates were collected by filtration, washed with water and dried to give powder of 7-[2-benzyloxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.03 g.).

Provenance & Evidence