Trichloroacetyl isocyanate → Cefuroxime Sodium

HRID 1277521Notes

Reaction equation

HRID 1277521 reaction equation
ClC(Cl)(Cl)[C:3]([N:5]=C=O)=[O:4].[O:10]1[CH:14]=[CH:13][CH:12]=[C:11]1/[C:15](=[N:33]/[O:34][CH3:35])/[C:16]([NH:18][C@@H:19]1[C:31](=[O:32])[N:21]2[C:22]([C:28]([OH:30])=[O:29])=[C:23]([CH2:26][OH:27])[CH2:24][S:25][C@H:20]12)=[O:17].C([O-])(=O)C.[Na+:40]>CO.C1COCC1.ClCCl>[CH3:35][O:34]/[N:33]=[C:15](\[C:16]([NH:18][C@@H:19]1[C:31](=[O:32])[N:21]2[C:22]([C:28]([O-:30])=[O:29])=[C:23]([CH2:26][O:27][C:3]([NH2:5])=[O:4])[CH2:24][S:25][C@H:20]12)=[O:17])/[C:11]1[O:10][CH:14]=[CH:13][CH:12]=1.[Na+:40]

Participants

7

Reactant 3

HCID 76400Trichloroacetyl isocyanateHCID 517045Sodium AcetateHCID 9800056(6R,7R)-7-(((2Z)-2-(2-Furanyl)-2-(methoxyimino)acetyl)amino)-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid

Product 1

HCID 23670318Cefuroxime Sodium

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of THF (60 ml), dichloromethane (25 ml), and trichloroacetyl isocyanate (6.2 ml) was protected from moisture and cooled to -10°.To the stirred mixture was added (6R,7R)-7-[Z-2-(fur-2-yl)-2-methyoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (10 g) in one charge followed by THF (20 ml). The mixture was stirred for 10 minutes at 0° to +5° to give a clear solution. Methanol (6.6 ml) was added, followed by portionwise addition of anhydrous sodium acetate (0.3 g) to raise the pH to 3.5. Charcoal (1 g) and filter aid (0.5 g Hyflo Supercel) were added and the mixture stirred at 10° for 20 minutes. Further anhydrous sodium acetate (5 g) was then added and the mixture stirred at 10° to 15° for 5 minutes by which time the pH had risen to 7.2. The charcoal, undissolved sodium acetate, and filter aid were removed by filtration and the filter bed washed with methanol (23 ml ) containing dichloromethane (10 ml). The filtrate and washes were combined, warmed to 25°, and left undisturbed at that temperature. Crystallisation commenced after 12 minutes. After 1 hour the mixture was stirred briefly and then left undisturbed for a further 11/2 hours. The crystalline material was collected by filtration, washed with THF (2×50 ml) and dried in vacuo at 35° to give sodium cefuroxime in a yield of 78.5%theory corrected for THF and sodium acetate.

Workup

  1. temperaturecooled to -10°
  2. additioncharge
  3. customto give a clear solution
  4. temperatureto raise the pH to 3.5
  5. filtrationCharcoal (1 g) and filter aid (0.5 g Hyflo Supercel)
  6. additionwere added
  7. stirringthe mixture stirred at 10° for 20 minutes
  8. additionFurther anhydrous sodium acetate (5 g) was then added
  9. stirringthe mixture stirred at 10° to 15° for 5 minutes by which time the pH
  10. filtrationThe charcoal, undissolved sodium acetate, and filter aid
  11. customwere removed by filtration
  12. washthe filter bed washed with methanol (23 ml )
  13. additioncontaining dichloromethane (10 ml)
  14. temperaturewarmed to 25°
  15. waitleft undisturbed at that temperature
  16. customCrystallisation
  17. waitcommenced after 12 minutes
  18. stirringAfter 1 hour the mixture was stirred briefly
  19. waitleft undisturbed for a further 11/2 hours
  20. filtrationThe crystalline material was collected by filtration
  21. washwashed with THF (2×50 ml)
  22. customdried in vacuo at 35°

Sources & evidence

ORD record
ord-33e39c1b3343494998da54e1505a50b8
Source dataset
uspto-grants-1981_07
Patent number
US04277601

Reaction notes

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