sodium (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate → HCID 178512423, compound

HRID 1073825Notes

Reaction equation

HRID 1073825 reaction equation
O[CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[C@H:13]([NH:14][C:15](=[O:63])/[C:16](/[C:38]3[N:39]=[C:40]([NH:43]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[S:41][CH:42]=3)=[N:17]\[O:18]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:12](=[O:64])[N:7]2[C:8]=1[C:9]([O-:11])=[O:10].[Na+].[C:66]([CH2:69][S:70][C:71]1[S:72][C:73]([SH:76])=[N:74][N:75]=1)(=[NH:68])[NH2:67]>CN(C=O)C>[C:66]([CH2:69][S:70][C:71]1[S:72][C:73]([S:76][CH2:2][C:3]2[CH2:4][S:5][C@@H:6]3[C@H:13]([NH:14][C:15](=[O:63])/[C:16](/[C:38]4[N:39]=[C:40]([NH2:43])[S:41][CH:42]=4)=[N:17]\[OH:18])[C:12](=[O:64])[N:7]3[C:8]=2[C:9]([OH:11])=[O:10])=[N:74][N:75]=1)(=[NH:67])[NH2:68]

Participants

4

Reactant 2

HCID 23676286sodium (6R,7R)-3-(hydroxymethyl)-8-oxo-7-[[(2Z)-2-[2-(tritylamino)-1,3-thiazol-4-yl]-2-trityloxyiminoacetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 178512424HCID 178512424, compound

Product 1

HCID 178512423HCID 178512423, compoundYield 27.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 906 mg of sodium 3-hydroxymethyl-7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-trityloxyiminoacetamido]-3-cephem-4-carboxylate and 309 mg of 2-amidinomethylthio -5-mercapto-1,3,4-thiadiazole in 7 ml of DMF was added 1.01 g of ethyl o-phenylenephosphate under ice-cooling and stirring. The reaction mixture was stirred at room temperature for 4 hours and subjected to a column chromatography on silica gel (100 g), being washed with acetone and eluted with acetone/water (9:1). The eluate was concentrated to dryness under reduced pressure, and there was added 20 ml of formic acid. The mixture was stirred at room temperature for 16 hours and then distilled to remove formic acid. To the residue was added a mixture of water and THF. The solution was washed with ethyl acetate, concentrated under reduced pressure and then subjected to a column chromatography on XAD-II (140 ml), being washed with water and eluted with 20% aqueous ethanol. The eluate was concentrated to 10 ml and the resultant precipitate was collected by filtration to give 160 mg of the title compound as pale yellow crystals.

Workup

  1. temperaturecooling
  2. stirringThe reaction mixture was stirred at room temperature for 4 hours
  3. washbeing washed with acetone
  4. washeluted with acetone/water (9:1)
  5. concentrationThe eluate was concentrated to dryness under reduced pressure, and there
  6. additionwas added 20 ml of formic acid
  7. stirringThe mixture was stirred at room temperature for 16 hours
  8. distillationdistilled
  9. customto remove formic acid
  10. additionTo the residue was added
  11. additiona mixture of water and THF
  12. washThe solution was washed with ethyl acetate
  13. concentrationconcentrated under reduced pressure
  14. washbeing washed with water
  15. washeluted with 20% aqueous ethanol
  16. concentrationThe eluate was concentrated to 10 ml
  17. filtrationthe resultant precipitate was collected by filtration

Sources & evidence

ORD record
ord-9210c92876dc42df9c95b90b1e5dfbf9
Source dataset
uspto-grants-1990_11
Patent number
US04971963

Reaction notes

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