Sodium Carbonate → 7-[2-(2-Formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 894791Notes

Reaction equation

HRID 894791 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16](=O)[NH2:17])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:24][CH:25]1[C:35](=[O:36])[N:27]2[C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH2:30][S:31][C@H:26]12.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1.O.CC(C)=O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]#[N:17])[C:10]([NH:24][CH:25]2[C:35](=[O:36])[N:27]3[C:28]([C:32]([OH:34])=[O:33])=[CH:29][CH2:30][S:31][C@H:26]23)=[O:12])[N:8]=1)=[O:2]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 538052302-(2-Formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid

Product 1

HCID 1317123307-[2-(2-Formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-cephem-4-carboxylic acidYield 49.4%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2-(2-Formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid (syn isomer, 1.2 g.), N,N-dimethylformamide (0.768 g.), phosphoryl chloride (1.61 g.) and tetrahydrofuran (2.4 ml.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. A suspension of 7-amino-3-cephem-4-carboxylic acid (0.89 g.) in a mixture of tetrahydrofuran (8.9 ml.), acetone (4.5 ml.) and water (4.5 ml.) was adjusted to pH 7 to 8 with 20% aqueous sodium carbonate. The activated acid solution was added to the solution at -5° to 0° C. while keeping at pH 7 to 8 and stirred at the same temperature for 30 minutes. The resultant solution was concentrated in vacuo, and water and ethyl acetate were added to the residue. The solution was adjusted to pH 2.5 and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diethyl ether, collected by filtration and dried to give 7-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.95 g.).

Workup

  1. customto give an activated acid solution
  2. additionThe activated acid solution was added to the solution at -5° to 0° C.
  3. concentrationThe resultant solution was concentrated in vacuo, and water and ethyl acetate
  4. additionwere added to the residue
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. filtrationcollected by filtration
  10. customdried

Sources & evidence

ORD record
ord-84e3ce6183774b8b83deb43c1f32cdd8
Source dataset
uspto-grants-1981_08
Patent number
US04284631

Reaction notes

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