Hydrochloric Acid → HCID 54473141, compound

Temperature

20 °C

A stirred solution of tert-butyl (6R,7R)-3-(2,4-dinitrostyryl)-7-phenylacetamido-ceph-3-em-4-carboxylate (67.41 g, purity 8% E-isomer, 81% Z-isomer, 105.9 mmol) in dichloromethane (1685 ml) was cooled to -25° C. Titanium tetrachloride (53 ml, 482 mmol) was added in 10 min and the temperature was brought to 0° C. After 105 min a chilled 2 M solution of hydrochloric acid in water was added at such a rate that the temperature remained under 10° C. The organic phase was separated and extracted with a 2 M solution of hydrochloric acid in water (2×1685 ml) and brine (1685 ml). The organic phase was concentrated under reduced pressure to give an orange foam. Crude product thus obtained was crystallized by dissolving in acetone (1350 ml) at 65° C. and adding water (675 ml). Crystallization was allowed to proceed for 16 h at 0° C. and the crystals were collected by filtration. Recrystallization of the product was performed by dissolving the material in acetone/acetic acid (2:1) at 53° C., removing solvent (1700 ml) by evaporation under reduced pressure and stirring for 16 h at 20° C. Crystals were collected by filtration, washed with acetic acid (300 ml) and ether (250 ml), and dried under vacuum at 45° C. to give 34.33 g (purity 99% E-isomer, 66.6 mmol; yield 63%) of (6R,7R)-3-(2,4-dinitrostyryl)-7-phenylacetamido-ceph-3-em-4-carboxylic acid as yellow crystals.

1. customwas brought to 0° C
2. customremained under 10° C
3. customThe organic phase was separated
4. extractionextracted with a 2 M solution of hydrochloric acid in water (2×1685 ml) and brine (1685 ml)
5. concentrationThe organic phase was concentrated under reduced pressure
6. customto give an orange foam
7. customCrude product thus obtained
8. customwas crystallized
9. dissolutionby dissolving in acetone (1350 ml) at 65° C.
10. additionadding water (675 ml)
11. customCrystallization
12. filtrationthe crystals were collected by filtration
13. customRecrystallization of the product
14. dissolutionby dissolving the material in acetone/acetic acid (2:1) at 53° C.
15. customremoving solvent (1700 ml)
16. customby evaporation under reduced pressure
17. filtrationCrystals were collected by filtration
18. washwashed with acetic acid (300 ml) and ether (250 ml)
19. customdried under vacuum at 45° C.

ORD record

ord-013137121e9c459a8c4f8c8e952dfb69

Source dataset

uspto-grants-2000_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06107481