反应详情

Diphenylmethyl (6R,7R)-7-amino-3-carbamoyloxymethylceph-3-em-4-carboxylate toluene-p-sulphonic acid salt (300.0 g, 0.44 mole), solvated with ca. 0.6 mole of chloroform, was added in portions over 30 minutes to a stirred mixture of trifluoroacetic acid (300 ml) and anisole (300 ml) immersed in a water-bath at 20°. The temperature of the mixture rose from 23° to 28° over the first 20 minutes but fell back to 26° by the end of the addition. The golden yellow solution was stirred for 1 hour, the temperature falling to 21°, and was then added to a stirred mixture of ethyl acetate (1.5 liters) and water (1.5 liters) immersed in an ice-bath. The pH of the stirred mixture was adjusted to 3.8 over 10 minutes with ammonia solution (S.G. 0.880), the temperature rising to 38°. The suspension was stirred and cooled to 10° over 1.25 hours and filtered. The cream solid was washed with water (750 ml) and ethyl acetate (4 × 200 ml) and dried in vacuo to give the title compound (115.6 g, 96.2%); λmax (pH6 phosphate) 265nm (ε7,750); purity by HPLC (high pressure liquid chromatography) 99.7%.

1. customimmersed in a water-bath at 20°
2. customrose from 23° to 28° over the first 20 minutes
3. additionfell back to 26° by the end of the addition
4. customfalling to 21°
5. customimmersed in an ice-bath
6. customrising to 38°
7. stirringThe suspension was stirred
8. temperaturecooled to 10° over 1.25 hours
9. filtrationfiltered
10. washThe cream solid was washed with water (750 ml) and ethyl acetate (4 × 200 ml)
11. customdried in vacuo