反应详情

A solution of 139.32 g (160 mmol) of a mixture consisting of the 2-[4-(p-toluenesulphonylthio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-(1-pyrrolidinyl)-crotonic acid diphenylmethyl ester and the corresponding isocrotonic acid ester in 1350 ml of dry acetonitrile is heated at 80° for approximately 6 hours under nitrogen until it is no longer possible to detect any starting material by thin layer-chromatography (silica gel; toluene/ethyl acetate 1:1). The heating bath is removed, the reaction mixture containing the 7β-phenoxyacetamido-3-(1-pyrrolidinyl)-3-cephem-4-carboxylic acid diphenylmethyl ester is left to cool for a further 11/2 hours, 550 ml of 0.1 N hydrochloric acid are added and the mixture is further stirred for 81/2 hours at room temperature. The reaction mixture is diluted with ethyl acetate, the water is separated off, the organic phase is washed twice with 2 N hydrochloric acid and three times with water, dried over sodium sulphate, concentrated by evaporation in vacuo and dried under a high vacuum. The residue, containing the 7β-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylic acid diphenylmethyl ester, is used in the next step without further purification.

1. customThe heating bath is removed
2. additionthe reaction mixture containing the 7β-phenoxyacetamido-3-(1-pyrrolidinyl)-3-cephem-4-carboxylic acid diphenylmethyl ester
3. waitis left
4. temperatureto cool for a further 11/2 hours, 550 ml of 0.1 N hydrochloric acid
5. additionare added
6. additionThe reaction mixture is diluted with ethyl acetate
7. customthe water is separated off
8. washthe organic phase is washed twice with 2 N hydrochloric acid and three times with water
9. dry with materialdried over sodium sulphate
10. concentrationconcentrated by evaporation in vacuo
11. customdried under a high vacuum
12. additionThe residue, containing the 7β-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylic acid diphenylmethyl ester
13. customis used in the next step without further purification