Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 434960Notes

Reaction equation

HRID 434960 reaction equation
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH3:18])[C:13]([OH:15])=O)[N:11]=1.C[Si](CC(N)=O)(C)C.Cl.[NH2:28][CH:29]1[C:49](=[O:50])[N:31]2[C:32]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])=[CH:33][CH2:34][S:35][C@H:30]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CC(C)=O.O1CCCC1.CN(C)C=O>[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH3:18])[C:13]([NH:28][CH:29]2[C:49](=[O:50])[N:31]3[C:32]([C:36]([O:38][CH2:39][C:40]4[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=4)=[O:37])=[CH:33][CH2:34][S:35][C@H:30]23)=[O:15])[N:11]=1

Participants

10

Reactant 5

HCID 24813Phosphorus oxychloride2×HCID 1252162-(2-Aminothiazole-4-yl)-2-methoxyiminoacetic acidHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 70362167p-Nitrobenzyl 7-amino-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 1317124504-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylateYield 60.4%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Phosphorus oxychloride (1.2 g.) was added all at once to a suspension of 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetic acid (syn-isomer: 1.23 g.) in ethyl acetate (12 ml.) at 5° C. and stirred at 4° to 6° C. for 30 minutes. Trimethylsilylacetamide (1.0 g.) was added to the solution and stirred at 4° to 6° C. for 30 minutes. Phosphorus oxychloride (1.2 g.) was added again to the solution and stirred for 15 minutes. And further, dimethylformamide (0.5 g.) was added all at once to the solution at 4° to 6° C. and stirred for 40 minutes to give a clear solution. On the other hand, p-nitrobenzyl 7-amino-3-cephem-4-carboxylate hydrochloride (1.9 g.) was added to a mixture of tetrahydrofuran (30 ml.) and acetone (10 ml.), and an aqueous solution (20 ml.) of sodium bicarbonate (0.6 g.) was added to the mixture. To the solution was added dropwise the solution obtained above at 0° to 5° C., pH 8.0. After stirring the mixture at -2° to 2° C., at pH 8.0 for 30 minutes, the insoluble substance was filtered out. The filtrate was extracted with ethyl acetate, and the extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was pulverized with diisopropyl ether to give p-nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn-isomer: 1.6 g.)

Workup

  1. stirringstirred at 4° to 6° C. for 30 minutes
  2. stirringstirred for 15 minutes
  3. stirringstirred for 40 minutes
  4. customto give a clear solution
  5. additionTo the solution was added dropwise the solution
  6. customobtained above at 0° to 5° C., pH 8.0
  7. stirringAfter stirring the mixture at -2° to 2° C.
  8. waitat pH 8.0 for 30 minutes
  9. filtrationthe insoluble substance was filtered out
  10. extractionThe filtrate was extracted with ethyl acetate
  11. washthe extract was washed with a saturated aqueous solution of sodium chloride
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-33910fefd63b498e84a4a6593095d43b
Source dataset
uspto-grants-1983_08
Patent number
US04399133

Reaction notes

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