Diketene → 3-Carbamoyloxymethyl-7-(3-oxo-4-bromobutyramido)-3-cephem-4-carboxylic acid

HRID 127111Notes

Reaction equation

HRID 127111 reaction equation
[CH2:1]=[C:2]1[O:5][C:4](=[O:6])[CH2:3]1.[Br:7]Br.[C:9]([O:12][CH2:13][C:14]1[CH2:15][S:16][C@@H:17]2[CH:24]([NH2:25])[C:23](=[O:26])[N:18]2[C:19]=1[C:20]([OH:22])=[O:21])(=[O:11])[NH2:10].C[Si](CC(N)=O)(C)C>C(Cl)Cl.C(OCC)(=O)C.O>[C:9]([O:12][CH2:13][C:14]1[CH2:15][S:16][C@@H:17]2[CH:24]([NH:25][C:4](=[O:6])[CH2:3][C:2](=[O:1])[CH2:5][Br:7])[C:23](=[O:26])[N:18]2[C:19]=1[C:20]([OH:22])=[O:21])(=[O:11])[NH2:10]

Participants

8

Reactant 4

HCID 12661DiketeneHCID 24408BromineHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 127847593-Carbamoyloxymethyl-7-amino-3-cephem-4-carboxylic acid

Product 1

HCID 886069703-Carbamoyloxymethyl-7-(3-oxo-4-bromobutyramido)-3-cephem-4-carboxylic acidYield 58.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-30 °C

Procedure

To a solution of 4-methylene-2-oxetanone (0.4 g.) in dried methylene chloride (5 ml.) was dropwise added a solution of bromine (0.75 g.) in dried methylene chloride (5 ml.) under cooling at -30° C., and then the mixed solution was stirred for 15 minutes at -10° to -5° C. Thus obtained solution was dropwise added to a solution of 3-carbamoyloxymethyl-7-amino-3-cephem-4-carboxylic acid (1.1 g.) and trimethylsilylacetamide (6.3 g.) in dried methylene chloride (15 ml.) under cooling at -20° C. The reaction temperature was gradually raised to at room temperature, and then the reaction mixture was stirred for 10 minutes at room temperature. After cooling the reaction mixture to at -20° C., water was added thereto, and then the mixture was stirred. The mixture was added a mixture of water (40 ml.) and ethyl acetate (80 ml.) with stirring, and the mixture was further stirred for 5 minutes, and then ethyl acetate layer was separated therefrom. The ethyl acetate layer was filtered, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then treated with activated carbon. After distillation of the solvent from the ethyl acetate layer, the residue was pulverized in diethyl ether, collected by filtration and then dried to give 3-carbamoyloxymethyl-7-(3-oxo-4-bromobutyramido)-3-cephem-4-carboxylic acid (1.02 g.)

Workup

  1. temperatureunder cooling at -20° C
  2. temperatureThe reaction temperature was gradually raised to at room temperature
  3. stirringthe reaction mixture was stirred for 10 minutes at room temperature
  4. additionwas added
  5. stirringthe mixture was stirred
  6. additionThe mixture was added
  7. stirringwith stirring
  8. stirringthe mixture was further stirred for 5 minutes
  9. customethyl acetate layer was separated
  10. filtrationThe ethyl acetate layer was filtered
  11. washwashed with a saturated aqueous solution of sodium chloride
  12. dry with materialdried over magnesium sulfate
  13. additiontreated with activated carbon
  14. distillationAfter distillation of the solvent from the ethyl acetate layer
  15. filtrationcollected by filtration
  16. customdried

Sources & evidence

ORD record
ord-f71ca80f50b742f9bc72641c4af69245
Source dataset
uspto-grants-1981_03
Patent number
US04254260

Reaction notes

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