Diisopropyl Ether → 7beta-formamido-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl) methyl}ammonio]methyl-3-cephem-4-carboxylate

HRID 1734261Notes

Reaction equation

HRID 1734261 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[CH2:10][C:9](=[O:11])[C:8]([OH:12])=[CH:7][N:6]=1)[CH3:3].C(C(CCCC)C([O-])=O)C.[Na+].[CH:24]([NH:26][C@@H:27]1[C:39](=[O:40])[N:29]2[C:30]([C:36]([OH:38])=[O:37])=[C:31]([CH2:34]Cl)[CH2:32][S:33][C@H:28]12)=[O:25].C(OC(C)C)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH:24]([NH:26][C@@H:27]1[C:39](=[O:40])[N:29]2[C:30]([C:36]([O-:38])=[O:37])=[C:31]([CH2:34][N+:2]([CH3:3])([CH3:1])[CH2:4][C:5]3[NH:6][CH:7]=[C:8]([OH:12])[C:9](=[O:11])[CH:10]=3)[CH2:32][S:33][C@H:28]12)=[O:25]

Participants

7

Reactant 4

HCID 7914Diisopropyl EtherHCID 23672331Sodium 2-ethylhexanoateHCID 677480632-(N,N-dimethylamino)methyl-5-hydroxy-4-pyridoneHCID 883005347beta-Formamido-3-chloromethyl-3-cephem-4carboxylic acid

Product 1

HCID 883998567beta-formamido-3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl) methyl}ammonio]methyl-3-cephem-4-carboxylateYield 43.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-(N,N-Dimethylamino) methyl-5-hydroxy-4-pyridone (15.85 g) was dissolved in N,N-dimethylformamide (238 ml) by addition of sodium 2-ethylhexanoate (10.44 g). To the resulting solution was added dropwise a cooled solution of 7β-formamido-3-chloromethyl-3-cephem-4-carboxylic acid (13.04 g) at 50C and the mixture was stirred for 2 hours at the same temperature. The mixture was added dropwise to a mixture of ethyl acetate (2.5 l) and diisopropyl ether (2.5 l) and the resulting precipitates were collected by filtration,washed three times with a mixture of ethyl acetate and diisopropyl ether (1:1) and dried in vacuo. The powder was poured into cold water (300 ml) and the mixture was adjusted to pH 3.0 with 1N hydrochloric acid. After the insoluble materials were filtered off, the filtrate was chromatographed on Diaion HP-20 (1300 ml) at 50° C. and the elution was carried out with 10% aqueous isopropyl alcohol. The eluate was lyophilized to give 7β-formamido- 3-[N,N-dimethyl-N-{(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl}ammonio]methyl-3-cephem-4-carboxylate (8.31 g).

Workup

  1. customthe resulting precipitates
  2. filtrationwere collected by filtration,washed three times with a mixture of ethyl acetate and diisopropyl ether (1:1)
  3. customdried in vacuo
  4. additionThe powder was poured into cold water (300 ml)
  5. filtrationAfter the insoluble materials were filtered off
  6. customthe filtrate was chromatographed on Diaion HP-20 (1300 ml) at 50° C.
  7. washthe elution

Sources & evidence

ORD record
ord-be6db3d89ab2479a837ca7fcd744a784
Source dataset
uspto-grants-1996_07
Patent number
US05532354

Reaction notes

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