Phosphorus oxychloride → 2-Methyl-7-[2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

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Reaction Conditions

Reaction Steps

To a solution of N,N-dimethylformamide (1.23 g) and ethyl acetate (9 ml) was added dropwise phosphorus oxychloride (2.58 g) at -10° to -5° C. with stirring, and the mixture was stirred for 30 minute at the same temperature. To the mixture were added 2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetic acid (syn isomer), which can be represented as 2-hexyloxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetic acid (syn isomer), (4.2 g) and ethyl acetate (33 ml), and the mixture was stirred for 30 minutes at -10° to -5° C. and then cooled to -20° C. Thus obtained solution was added to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (3 g) and trimethylsilylacetamide (11 g) in ethyl acetate (33 ml), with stirring under cooling to -10° C. The mixture was stirred for 30 minutes at -10° C. and thereto was added water 50 ml. The mixture was extracted twice with ethyl acetate. The combined extracts were washed with an aqueous solution of sodium chloride and the precipitates were collected by filtration and then dried to give 2-methyl-7-[2-hexyloxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-hexyloxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (4.3 g). The filtrate was evaporated to give further the same object compound (1.15 g).

Provenance & Evidence