反应详情

2.09 g of p-toluenesulphonic acid monohydrate are added to a suspension of 5.0 g of 7β-amino-3-(1-methyl-5-tetrazolylthiomethyl)-3-cephem-4-carboxylic acid (U.S. Pat. No. 3,516,997) in 200 ml of methanol, whilst stirring; this slowly produces a clear solution, which is concentrated under reduced pressure. Diethyl ether is added and the p-toluenesulphonic acid salt of 7β-amino-3-(1-methyl-5-tetrazolylthiomethyl)-3-cephem-4carboxylic acid is filtered off. The salt is dissolved in 100 ml of dioxane and 2.5 g of diphenyldiazomethane are added in portions to the solution. The mixture is stirred for 18 hours at room temperature and concentrated under reduced pressure; 100 ml of an 0.1 N aqueous sodium bicarbonate solution are added to the residue and the mixture is extracted with twice 100 ml of ethyl acetate. The organic extracts are washed successively with water and with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and concentrated. The crystallisation from diethyl ether gives 7β-amino-3-(1-methyl-5-tetrazolylthiomethyl)-3-cephem-4-carboxylic acid diphenylmethyl ester, thin layer chromatogram (silica gel): Rf=0.21 (system: chloroform/ethyl acetate/acetic acid, 80:19:1); ultraviolet absorption spectrum (ethanol): λmax =269 mμ (ε=6,400); infrared absorption spectrum (in methylene chloride); characteristic bands at 2.93μ, 5.60μ and 6.15μ.

1. customthis slowly produces a clear solution, which
2. concentrationis concentrated under reduced pressure
3. additionDiethyl ether is added
4. filtrationthe p-toluenesulphonic acid salt of 7β-amino-3-(1-methyl-5-tetrazolylthiomethyl)-3-cephem-4carboxylic acid is filtered off
5. dissolutionThe salt is dissolved in 100 ml of dioxane
6. addition2.5 g of diphenyldiazomethane are added in portions to the solution
7. concentrationconcentrated under reduced pressure
8. addition100 ml of an 0.1 N aqueous sodium bicarbonate solution are added to the residue
9. extractionthe mixture is extracted with twice 100 ml of ethyl acetate
10. washThe organic extracts are washed successively with water and with a saturated aqueous sodium chloride solution
11. dry with materialdried over magnesium sulphate
12. concentrationconcentrated
13. customThe crystallisation from diethyl ether