Sodium Chloride → 7-[2-methoxyimino-2-(4-thiazolyl)-acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 463943Notes

Reaction equation

HRID 463943 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[CH:15][S:16][CH:17]=1)[C:10]([OH:12])=O.[NH2:18][CH:19]1[C:39](=[O:40])[N:21]2[C:22]([C:36]([OH:38])=[O:37])=[C:23]([CH2:26][S:27][C:28]3[N:32]([CH2:33][CH:34]=[CH2:35])[N:31]=[N:30][N:29]=3)[CH2:24][S:25][C@H:20]12.C[Si](CC(N)=O)(C)C.[Cl-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:14]=[CH:15][S:16][CH:17]=1)[C:10]([NH:18][CH:19]1[C:39](=[O:40])[N:21]2[C:22]([C:36]([OH:38])=[O:37])=[C:23]([CH2:26][S:27][C:28]3[N:32]([CH2:33][CH:34]=[CH2:35])[N:31]=[N:30][N:29]=3)[CH2:24][S:25][C@H:20]12)=[O:12]

Participants

9

Reactant 6

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 538568222-(Thiazol-4-yl)-2-methoxyiminoacetic acidHCID 704326537-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317121957-[2-methoxyimino-2-(4-thiazolyl)-acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 90.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-25 °C

Procedure

To dimethylformamide (0.2 g) was added dropwise phosphorus oxychloride (0.4 g) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. and then suspended in ethyl acetate (10 ml). To the suspension was added 2-methoxyimino-2-(4-thiazolyl)acetic acid (syn isomer) (0.4 g) under stirring and ice-cooling and then stirred for 30 minutes under ice-cooling. Thus obtained solution was added to a solution, which was prepared by stirring a mixture of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (0.76 g) and trimethylsilylacetamide (2.3 g) in ethyl acetate (20 ml), under cooling to -25° C. The mixture was stirred for 1 hour at -20° C. to -10° C., and a saturated aqueous solution of sodium chloride (100 ml) was added thereto. Thus obtained mixture was adjusted to pH 7.5 with 20% aqueous solution of sodium carbonate, and the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and adjusted to pH 2 with 10% hydrochloric acid, and then extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then evaporated. The residue was pulverized in diethyl ether, collected by filtration and then dried to give 7-[2-methoxyimino-2-(4-thiazolyl)-acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.01 g).

Workup

  1. temperatureice-cooling
  2. stirringthe mixture was stirred for 30 minutes at 40° C.
  3. stirringunder stirring
  4. temperatureice-cooling
  5. stirringstirred for 30 minutes under ice-
  6. temperaturecooling
  7. additionThus obtained solution was added to a solution, which
  8. customwas prepared
  9. stirringby stirring
  10. stirringThe mixture was stirred for 1 hour at -20° C. to -10° C.
  11. customthe aqueous layer was separated
  12. additionTo the aqueous layer was added ethyl acetate
  13. extractionextracted with ethyl acetate
  14. washThe ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride
  15. dry with materialdried over magnesium sulfate
  16. customevaporated
  17. filtrationcollected by filtration
  18. customdried

Sources & evidence

ORD record
ord-2907729067b548e495b9b7d61739a118
Source dataset
uspto-grants-1985_10
Patent number
US04544751

Reaction notes

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