Sodium Chloride → HCID 131713390, compound

HRID 1388415Notes

Reaction equation

HRID 1388415 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[CH:14]=1)[C:10]([OH:12])=O.[NH2:20][CH:21]1[C:39](=[O:40])[N:23]2[C:24]([C:36]([OH:38])=[O:37])=[C:25]([CH2:28][S:29][C:30]3[N:34]([CH3:35])[N:33]=[N:32][N:31]=3)[CH2:26][S:27][C@H:22]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[Cl-].[Na+]>C(OCC)(=O)C.C(Cl)Cl.CN(C)C=O>[CH3:6][O:7][N:8]=[C:9]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[CH:14]=1)[C:10]([NH:20][CH:21]1[C:39](=[O:40])[N:23]2[C:24]([C:36]([OH:38])=[O:37])=[C:25]([CH2:28][S:29][C:30]3[N:34]([CH3:35])[N:33]=[N:32][N:31]=3)[CH2:26][S:27][C@H:22]12)=[O:12]

Participants

9

Reactant 5

HCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 11708267BistrimethylsilylacetamidHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 543905512-Methoxyimino-2-(3-hydroxyphenyl)acetic acid

Product 1

HCID 131713390HCID 131713390, compoundYield 63.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

A mixture of dimethylformamide (2.81 g.) and phosphorus oxychloride (5.36 g.) was warmed at 40° C. for 1 hour. After cooling, methylene chloride (60 ml.) was added thereto and disilled off. To the residue was added dry ethyl acetate (50 ml.). Then, 2-methoxyimino-2-(3-hydroxyphenyl)acetic acid (syn isomer) (6.83 g.) was added thereto at 5° C. with stirring under ice-cooling. The resultant mixture was then stirred for 50 minutes at the same temperature. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (11.5 g.) and bis(trimethylsilyl)acetamide (28.4 g.) were dissolved in dry ethyl acetate (150 ml.) and stirred under cooling, to which was at a time added the above obtained solution at -40° C. After stirring for 2 hours at -30° to -20° C., a saturated sodium chloride aqueous solution (100 ml.) was added at -20° C. to the reaction mixture. The mixture was stirred for 5 minutes. The precipitates were filtered off and ethyl acetate layer in the filtrate was separated. The aqueous layer was extracted twice with ethyl acetate (50 ml.). Ethyl acetate layer separated from the filtrate and the extracts were combined. The combined ethyl acetate solution was washed with a saturated sodium chloride aqueous solution (50 ml.). To the ethyl acetate layer was added activated charcoal and the mixture was stirred for 5 minutes and filtered. Water (100 ml.) was added to the filtrate and the resulting mixture was adjusted to pH 7 with an aqueous solution of sodium bicarbonate. The aqueous layer was separated and washed with methylene chloride. After the aqueous layer was separated, methylene chloride was removed from the aqueous layer by bubbling of nitrogen gas under ice-cooling. After filtration, the aqueous layer was adjusted to pH 2 with 10% hydrochloric acid with stirring and ice-cooling. Precipitating crystals were collected by filtration, washed with water and dried to give 7-[2-methoxyimino-2-(3-hydroxyphenyl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (11.3 g.).

Workup

  1. temperatureAfter cooling
  2. temperaturecooling
  3. stirringstirred
  4. temperatureunder cooling, to which
  5. additionadded the above obtained solution at -40° C
  6. stirringAfter stirring for 2 hours at -30° to -20° C.
  7. stirringThe mixture was stirred for 5 minutes
  8. filtrationThe precipitates were filtered off
  9. customethyl acetate layer in the filtrate was separated
  10. extractionThe aqueous layer was extracted twice with ethyl acetate (50 ml.)
  11. customEthyl acetate layer separated from the filtrate
  12. washThe combined ethyl acetate solution was washed with a saturated sodium chloride aqueous solution (50 ml.)
  13. additionTo the ethyl acetate layer was added
  14. stirringthe mixture was stirred for 5 minutes
  15. filtrationfiltered
  16. additionWater (100 ml.) was added to the filtrate
  17. customThe aqueous layer was separated
  18. washwashed with methylene chloride
  19. customAfter the aqueous layer was separated
  20. custommethylene chloride was removed from the aqueous layer
  21. customby bubbling of nitrogen gas under ice-
  22. temperaturecooling
  23. filtrationAfter filtration
  24. stirringwith stirring
  25. temperatureice-cooling
  26. customPrecipitating crystals
  27. filtrationwere collected by filtration
  28. washwashed with water
  29. customdried

Sources & evidence

ORD record
ord-fbc405ddb9fd46e58ab8dc45b993acbd
Source dataset
uspto-grants-1984_02
Patent number
US04431643

Reaction notes

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