Sodium Carbonate → Cefmenoxime sodium

Participants

Reaction Steps

In a solvent mixture of 50 ml water and 35 ml tetrahydrofuran were dissolved 1.64 g of 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid and 1.68 g of sodium hydrogen carbonate. To this solution was added a solution of 2.1 g 4-bromo-2-methoxyimino-3-oxobutyryl chloride in 15 ml tetrahydrofuran and the mixture was stirred at 20°-25° C. for 5 minutes. Then, a solution of 1.52 g thiourea in 20 ml water was added thereto and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was adjusted to pH 7.0 with 20% aqueous sodium carbonate solution and concentrated under reduced pressure. The concentrate was subjected to column chromatography using Diaion HP-40 (Mitsubishi Chemical Industries, Ltd.) and elution was carried out with 400 ml of water-isopropyl alcohol (9:1, v/v). The eluate was lyophilized to give 2.35 g of sodium 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate. Yield 88.2%. Analysis by high-performance liquid chromatography showed that the proportion of the (E)-isomer was not more than 1% of the (Z)-isomer.

Provenance & Evidence