Ethyl Acetate → 7beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylate

HRID 5517Notes

Reaction equation

HRID 5517 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:32][O:33][C:34]([C:37]([OH:39])=[O:38])([CH3:36])[CH3:35])[C:15]([NH:17][C@@H:18]2[C:30](=[O:31])[N:20]3[C:21]([C:27]([OH:29])=[O:28])=[C:22]([CH2:25]Cl)[CH2:23][S:24][C@H:19]23)=[O:16])[N:10]=1.[CH3:40][N:41]([CH2:43][C:44]1[CH2:49][C:48](=[O:50])[C:47]([OH:51])=[CH:46][N:45]=1)[CH3:42].C(OCC)(=O)C>CN(C)C=O>[NH2:8][C:9]1[S:13][N:12]=[C:11]([C:14](=[N:32][O:33][C:34]([C:37]([OH:39])=[O:38])([CH3:36])[CH3:35])[C:15]([NH:17][C@@H:18]2[C:30](=[O:31])[N:20]3[C:21]([C:27]([O-:29])=[O:28])=[C:22]([CH2:25][N+:41]([CH3:42])([CH3:40])[CH2:43][C:44]4[NH:45][CH:46]=[C:47]([OH:51])[C:48](=[O:50])[CH:49]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[N:10]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 677480632-(N,N-dimethylamino)methyl-5-hydroxy-4-pyridoneHCID 1317181257beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate

Product 1

HCID 1317181237beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylateYield 29.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylic acid trifluoroacetate (syn isomer) (1.0 g) in N,N-dimethylformamide (10 ml) was added 2-(N,N-dimethylamino)methyl-5-hydroxy-4pyridone (1.09 g). After being stirred for 5 hours at ambient temperature, the mixture was poured into ethyl acetate (150 ml). The resulting precipitate was collected by filtration, washed with ethyl acetate and dried under reduced pressure. The precipitate was suspended in water (50 ml) at pH 2.0 and stirred for 30 minutes. After removal of insoluble material, the aqueous solution was subjected to column chromatography on Diaion HP-20. The column was washed with water and the elution was carried out with 30% aqueous methanol. The fractions containing desired product was combined and methanol was evaporated in vacuo. The resulting aqueous layer was lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4carboxylate (syn isomer) (0.30 g) as a powder.

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. washwashed with ethyl acetate
  3. customdried under reduced pressure
  4. stirringstirred for 30 minutes
  5. customAfter removal of insoluble material
  6. washThe column was washed with water
  7. washthe elution
  8. additionThe fractions containing desired product
  9. custommethanol was evaporated in vacuo

Sources & evidence

ORD record
ord-a1996d3323e84ceebe125fe52c63369e
Source dataset
uspto-grants-1993_09
Patent number
US05244890

Reaction notes

Loading…