Dichloromethane → Cefuroxime Sodium

HRID 1277522Notes

Reaction equation

HRID 1277522 reaction equation
ClCCl.ClC(Cl)(Cl)[C:6]([N:8]=C=O)=[O:7].[O:13]1[CH:17]=[CH:16][CH:15]=[C:14]1/[C:18](=[N:36]/[O:37][CH3:38])/[C:19]([NH:21][C@@H:22]1[C:34](=[O:35])[N:24]2[C:25]([C:31]([OH:33])=[O:32])=[C:26]([CH2:29][OH:30])[CH2:27][S:28][C@H:23]12)=[O:20].C(C(CCCC)C([O-])=O)C.[Na+:49]>C1COCC1.C(O)CO>[CH3:38][O:37]/[N:36]=[C:18](\[C:19]([NH:21][C@@H:22]1[C:34](=[O:35])[N:24]2[C:25]([C:31]([O-:33])=[O:32])=[C:26]([CH2:29][O:30][C:6]([NH2:8])=[O:7])[CH2:27][S:28][C@H:23]12)=[O:20])/[C:14]1[O:13][CH:17]=[CH:16][CH:15]=1.[Na+:49]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 76400Trichloroacetyl isocyanateHCID 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 acidHCID 23672331Sodium 2-ethylhexanoate

Product 1

HCID 23670318Cefuroxime Sodium

Reagents, catalysts & solvents 2

HCID 174Ethylene GlycolSolventHCID 8028TetrahydrofuranSolvent3×

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-methoxyiminoacetamido]-3-hydroxymethylceph-3-em-4-carboxylic acid (10 g) in one charge followed by THF (20 ml). The temperature was controlled in the range 0° to +5° and the mixture stirred for 10 minutes. Ethane-1,2-diol (15 ml) was added followedby a solution of sodium 2-ethylhexanoate (10 g) in THF (20 ml) to raise thepH to 7.3. The mixture was warmed to 25° and left undisturbed for 1 hour. The mixture was then stirred briefly and left undisturbed for a further hour. The crystalline material which had separated from the mixture was collected by filtration, washed with THF (2×50 ml), and dried in vacuo at 35° to yield sodium cefuroxime (10.76 g) THF solvate. The isolated product was shown by G.L.C. to contain 8.8% w/w of THF and 0.56% w/w of ethane-1,2-diol.

Workup

  1. temperaturecooled to -10°
  2. additioncharge
  3. customwas controlled in the range 0° to +5°
  4. temperatureto raise thepH to 7.3
  5. temperatureThe mixture was warmed to 25°
  6. waitleft undisturbed for 1 hour
  7. stirringThe mixture was then stirred briefly
  8. waitleft undisturbed for a further hour
  9. customThe crystalline material which had separated from the mixture
  10. filtrationwas collected by filtration
  11. washwashed with THF (2×50 ml)
  12. customdried in vacuo at 35°

Sources & evidence

ORD record
ord-594c83a070164b01b0d66aeb81c34e87
Source dataset
uspto-grants-1981_07
Patent number
US04277601

Reaction notes

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