反应详情

温度

20 °C

To a stirred solution of p-nitrobenzyl α-(3-phenoxymethyl-7-oxo-4-thia-2,6-diazabicyclo(3,2,0)hept-2-en-6-yl)-α-(1-hydroxyethylidene)acetate (9.38 g.) in tetrahydrofuran (120 ml.) under a nitrogen atmosphere at 20° C. was added triethylamine (3.21 ml.) followed by phenyl phenylphosphonochloridate (5.82 g.) After stirring for 2 hours at 20° C., the reaction mixture was cooled to 0° C. and morpholine (4.01 ml.) added. After stirring for 2.5 hours at 0°-5° C., the mixture was cooled to -30° to -35° C. and pyridine (1.62 ml.) added followed by dropwise addition of bromine (1.00 ml.) over a period of 10 minutes. The reaction mixture was stirred at -30° to -35° C. for 20 minutes and 5% hydrochloric acid (144 ml.) added. After stirring at 20° C. overnight the mixture was extracted with dichloromethane and the extracts washed with water and saturated sodium chloride solution, dried with magnesium sulphate and evaporated to dryness. The residue was dissolved in glacial acetic acid (10 ml.) and the resulting solution stirred for approximately 10 minutes to crystallise the product. The crystallisation was completed by addition of isopropanol (120 ml.) over 0.5 hour. The crystals were isolated by filtration, washed with isopropanol and dried in vacuo at 40° C. overnight. The yield of p-nitrobenzyl 7-phenoxyacetamido-3-hydroxy-3-cephem-4-carboxylate acetic acid solvate was 8.29 g. (76%).

1. temperaturethe reaction mixture was cooled to 0° C.
2. stirringAfter stirring for 2.5 hours at 0°-5° C.
3. temperaturethe mixture was cooled to -30° to -35° C.
4. stirringThe reaction mixture was stirred at -30° to -35° C. for 20 minutes
5. stirringAfter stirring at 20° C. overnight the mixture
6. extractionwas extracted with dichloromethane
7. washthe extracts washed with water and saturated sodium chloride solution
8. dry with materialdried with magnesium sulphate
9. customevaporated to dryness
10. dissolutionThe residue was dissolved in glacial acetic acid (10 ml.)
11. stirringthe resulting solution stirred for approximately 10 minutes
12. customto crystallise the product
13. customThe crystallisation
14. additionwas completed by addition of isopropanol (120 ml.) over 0.5 hour
15. customThe crystals were isolated by filtration
16. washwashed with isopropanol
17. customdried in vacuo at 40° C. overnight