Tetrahydrofuran → Desacetylcefotaxime

Participants

Reaction Steps

In 800 ml of water-tetrahydrofuran (briefly, THF) (1:1) is suspended 16.9 g of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, and with ice-cooling and stirring, 27.72 g of sodium hydrogen carbonate is added. Then, 29.4 g of 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetyl chloride hydrochloride is added gradually thereto and the mixture is stirred for 30 minutes. To this reaction mixture are added 150 ml of water and 200 ml of ethyl acetate and the water layer is separated. Under ice-cooling and stirring, this water layer is adjusted to pH 7.0 with 1N-hydrochloric acid. Under stirring at room temperature, 18.9 g of sodium N-methyldithiocarbamate is added gradually to thereby eliminate the aminoprotective group (This is confirmed by TLC). To the reaction mixture is added 300 ml of ethyl acetate and the water layer is separated and concentrated under reduced pressure to 70 ml. The residue is chromatographed on a column of XAD-II (1 l) and eluted with water. The fractions rich in the desired compound are pooled and concentrated to 100 ml, and with ice-cooling and stirring, the residue is adjusted to pH 2.5 with 4N-hydrochloric acid. The resulting crystals are collected by filtration, washed with 100 ml of water, 50 ml of ethyl acetate and 50 ml of THF, and dried under reduced pressure. The above procedure yields 19.3 g of 7β-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid

Provenance & Evidence