Formamide → (6R,7R)-7-Amino-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid

Participants

Reaction Steps

To the mixture of 230 mg of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, 174 mg of 5-mercapto-1-methyl-1H-tetrazole, 4 ml of formamide and 1 ml of acetonitrile was added 253 mg of triethylamine under stirring and cooling with ice bath. To the resulting solution were added a solution of 650 mg of methyl o-phenylene phosphate in 2 ml of methylene chloride and 5 ml of acetonitrile under stirring and cooling at -10° C. to 0° C., followed by stirring for 0.5 hour at 0° C. to 5° C. The resulting precipitate was collected by filtration, washed with 5 ml of acetonitrile and suspended in a mixed solution of 6 ml of water and 2 ml of acetonitrile. To this suspension was added about 0.1 ml of 35% hydrochloric acid to obtain a clear solution. After adjusting the pH of the solution to 4 by addition of 25% ammonia-water under cooling with ice bath, the resulting crystals were collected by filtration, washed with 2 ml of cold water and dried in vacuo to give 280 mg (yield 85.3%) of 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid.

Provenance & Evidence