Phosphorus oxychloride → 7-(2-Methoxyimino-3,3-ethylenedioxy-4-bromobutyramido)-3-hydroxycepham-4-carboxylic acid

HRID 1702071Notes

Reaction equation

HRID 1702071 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1([O:19][CH2:18][CH2:17][O:16]1)[CH2:14][Br:15])[C:10]([OH:12])=O.[NH2:20][CH:21]1[C:32](=[O:33])[N:23]2[CH:24]([C:29]([OH:31])=[O:30])[CH:25]([OH:28])[CH2:26][S:27][C@H:22]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:6][O:7][N:8]=[C:9]([C:13]1([O:19][CH2:18][CH2:17][O:16]1)[CH2:14][Br:15])[C:10]([NH:20][CH:21]1[C:32](=[O:33])[N:23]2[CH:24]([C:29]([OH:31])=[O:30])[CH:25]([OH:28])[CH2:26][S:27][C@H:22]12)=[O:12]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 13072520(6R)-7-amino-3-hydroxy-8-oxo-5-thia-1-azabicyclo[4.2.0]octane-2-carboxylic acidHCID 536757272-Methoxyimino-3,3-ethylenedioxy-4-bromobutyric acid

Product 1

HCID 867380907-(2-Methoxyimino-3,3-ethylenedioxy-4-bromobutyramido)-3-hydroxycepham-4-carboxylic acidYield 85.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Phosphorus oxychloride (0.5 ml.) was added to a solution of N,N-dimethylformamide (0.42 ml) in dry ethyl acetate (1 ml.) under cooling, and 2-methoxyimino-3,3-ethylenedioxy-4-bromobutyric acid (syn isomer, 1.2 g.) was added thereto under cooling and stirred at the same temperature. The solution was added to a stirred solution of 7-amino-3-hydroxycepham-4-carboxylic acid (1.0 g.) and trimethylsilylacetamide (6.0 g.) in dry ethyl acetate (50 ml.), at -20° C. and stirred at the same temperature for an hour. Ethyl acetate (20 ml.) and water (10 ml) were added to the resultant solution and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (20 ml.). The ethyl acetate layer and the extract were combined, and extracted with a saturated aqueous solution of sodium bicarbonate (20 ml.), and water (20 ml.) successively. After ethyl acetate (50 ml) was added thereto, the aqueous solution was adjusted to pH 2.0 with 6 N hydrochloric acid, and the ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (25 ml×2). The ethyl acetate layer and the extract were combined, washed with a saturated sodium chloride aqueous solution and dried over magnesium sulfate. After evaporating the solvent in vacuo, the residue was pulverized with diisopropyl ether. The precipitates were collected by filtration to give 7-(2-methoxyimino-3,3-ethylenedioxy-4-bromobutyramido)-3-hydroxycepham-4-carboxylic acid (syn isomer, 1.8 g.).

Workup

  1. temperatureunder cooling
  2. temperatureunder cooling
  3. stirringstirred at the same temperature for an hour
  4. customthe ethyl acetate layer was separated
  5. extractionThe aqueous layer was extracted with ethyl acetate (20 ml.)
  6. extractionextracted with a saturated aqueous solution of sodium bicarbonate (20 ml.), and water (20 ml.) successively
  7. additionAfter ethyl acetate (50 ml) was added
  8. customthe ethyl acetate layer was separated
  9. extractionThe aqueous layer was extracted with ethyl acetate (25 ml×2)
  10. washwashed with a saturated sodium chloride aqueous solution
  11. dry with materialdried over magnesium sulfate
  12. customAfter evaporating the solvent in vacuo
  13. filtrationThe precipitates were collected by filtration

Sources & evidence

ORD record
ord-8f8da6ef621c4ab1a5aa9ff824e4ed11
Source dataset
uspto-grants-1983_04
Patent number
US04379922

Reaction notes

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