Hydrochloric Acid → HCID 131718135, compound

HRID 5526Notes

Reaction equation

HRID 5526 reaction equation
Cl.C([NH:4][C:5]1[S:6][CH:7]=[C:8]([C:10](=[N:41][O:42][CH2:43][C:44]([O:46]C(C)(C)C)=[O:45])[C:11]([NH:13][C@@H:14]2[C:39](=[O:40])[N:16]3[C:17]([C:36]([O-:38])=[O:37])=[C:18]([CH2:21][N+:22]4([CH3:35])[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]4)[CH2:19][S:20][C@H:15]23)=[O:12])[N:9]=1)=O.Cl.C(OCC)(=O)C>CO>[NH2:4][C:5]1[S:6][CH:7]=[C:8]([C:10](=[N:41][O:42][CH2:43][C:44]([OH:46])=[O:45])[C:11]([NH:13][C@@H:14]2[C:39](=[O:40])[N:16]3[C:17]([C:36]([O-:38])=[O:37])=[C:18]([CH2:21][N+:22]4([CH3:35])[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]4)[CH2:19][S:20][C@H:15]23)=[O:12])[N:9]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 131718137HCID 131718137, compound

Product 1

HCID 131718135HCID 131718135, compoundYield 26.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 7β-[2-(2-formamidothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-(1-methyl-4-tert-butoxycarbonyl-1-piperazinio)methyl-3-cephem-4-carboxylate hydrochloride (syn isomer) (4.02 g) in methanol (12 ml) was added conc. hydrochloric acid (4.4 ml) at 10° C. The resulting solution was warmed to room temperature and stirred for 4.5 hours. The mixture was pulverized with ethyl acetate (800 ml) and the powder was collected by filtration, washed with ethyl acetate and dried in vacuo. The powder (3.68 g) was suspended in a mixture of dichloromethane (12 ml) and anisole (4 ml), and trifluoroacetic acid (8 ml) was added thereto. After being stirred at room temperature for 3.5 hours, the mixture was pulverized with diisopropyl ether (800 ml) and the powder was collected by filtration and washed with diisopropyl ether. The powder was suspended in a mixture of water (100 ml) and ethyl acetate (30 ml) and adjusted with a saturated aqueous solution of sodium bicarbonate. After removal of the insoluble materials, the aqueous layer was separated, adjusted to pH 4 with 1N hydrochloric acid and chromatographed on Diaion HP-20 (250 ml). The elution was carried out with 10% aqueous isopropyl alcohol. The eluate was lyophilized to give 7β-[2-(2-aminothiazol- 4-yl)-2-carboxymethoxyiminoacetamido]-3-(1-methyl-1-piperazinio)methyl-3-cephem-4-carboxylate (syn isomer) (763 mg).

Workup

  1. filtrationthe powder was collected by filtration
  2. washwashed with ethyl acetate
  3. customdried in vacuo
  4. additionThe powder (3.68 g) was suspended in a mixture of dichloromethane (12 ml) and anisole (4 ml), and trifluoroacetic acid (8 ml)
  5. additionwas added
  6. stirringAfter being stirred at room temperature for 3.5 hours
  7. filtrationthe powder was collected by filtration
  8. washwashed with diisopropyl ether
  9. additionThe powder was suspended in a mixture of water (100 ml) and ethyl acetate (30 ml)
  10. customAfter removal of the insoluble materials
  11. customthe aqueous layer was separated
  12. customchromatographed on Diaion HP-20 (250 ml)
  13. washThe elution

Sources & evidence

ORD record
ord-fb89a90e5efb421fbb23e563617fd178
Source dataset
uspto-grants-1993_09
Patent number
US05244890

Reaction notes

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