Phosphorus oxychloride → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To dimethylformamide (0.12 g.) was dropwise added phosphorus oxychloride (0.29 g.) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. and then cooled to -20° C. To the mixture was added all at once a solution of 2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetic acid, which can be represented as 2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro-1,3-thiazol-4-yl)acetic acid, (0.52 g.) in ethyl acetate (7 ml.) at -20° C. with stirring, and then the mixture was stirred for 30 minutes at -20° to -10° C. Thus obtained mixture was added all at once to the solution prepared in the similar manner as in Example 1 from 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (0.51 g.), bis(trimethylsilyl)acetamide (1.5 ml.) and ethyl acetate (10 ml.), at -40° C. The mixture was stirred for 30 minutes at the same temperature and further stirred for 1.5 hours at -20° to -10° C. After the reaction, the reaction mixture was poured into 5% sodium bicarbonate aqueous solution (20 ml.). The mixture was washed with ethyl acetate, and the aqueous layer was separated therefrom. Thus obtained aqueous layer was post-treated in a similar manner as that of example 5 to give 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (0.41 g.)

Provenance & Evidence