Ethyl Acetate → Desacetylcefotaxime

Participants

Reaction Steps

7β-Amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, 16.97 g, is suspended in a mixture of 400 ml of water and 400 ml of tetrahydrofuran, to which 27.72 g of sodium hydrogen carbonate is added with stirring under ice cooling. Then 29.4 g of 2-(2-chloroacetamidothiazol-4-yl)-2(Z)-methoxyiminoacetyl chloride hydrochloride is added in small portions and stirred for 30 minutes. To the reaction mixture 150 ml of water and 200 ml of ethyl acetate are added and the aqueous layer is separated, and then brought to pH 7 with 1N hydrochloric acid under ice cooling. To this, with stirring at room temperature, 18.9 g of sodium N-methyldithiocarbamate is added in small portions and stirred for further 3 hours. The reaction mixture is washed with 300 ml of ethyl acetate, concentrated to 70 ml and purified by column chromatography (on 1 liter of XAD-2, eluted with water). The eluate is concentrated to 100 ml and brought to pH 2.5 with 4N hydrochloric acid under ice cooling, and the deposited crystals are collected by filtration. The crystals are washed successively with 100 ml of water, 50 ml of ethyl acetate, and 50 ml of tetrahydrofuran, and dried under reduced pressure to give 19.3 g of the desired compound.

Provenance & Evidence