Phosphorus oxychloride → 7-[2-Methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid

HRID 543847Notes

Reaction equation

HRID 543847 reaction equation
[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:12]=[C:11]([NH2:13])[S:10][N:9]=1)[C:5]([OH:7])=O.P(Cl)(Cl)(Cl)=O.[NH2:19][CH:20]1[C:35](=[O:36])[N:22]2[C:23]([C:32]([OH:34])=[O:33])=[C:24]([CH2:27][O:28][C:29](=[O:31])[NH2:30])[CH2:25][S:26][C@H:21]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C)C=O>[CH3:1][O:2][N:3]=[C:4]([C:8]1[N:12]=[C:11]([NH2:13])[S:10][N:9]=1)[C:5]([NH:19][CH:20]1[C:35](=[O:36])[N:22]2[C:23]([C:32]([OH:34])=[O:33])=[C:24]([CH2:27][O:28][C:29](=[O:31])[NH2:30])[CH2:25][S:26][C@H:21]12)=[O:7]

Participants

8

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 127847593-Carbamoyloxymethyl-7-amino-3-cephem-4-carboxylic acidHCID 533952072-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid

Product 1

HCID 1317122397-[2-Methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetamido]-3-carbamoyloxymethyl-3-cephem-4-carboxylic acidYield 52.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-methoxyimino-2-(5-amino-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer)(1.01 g) and phosphorus oxychloride (3.06 g) in methylene chloride (25 ml) was stirred for 2 hours at ambient temperature, cooled to 0° C. and thereto was added N,N-dimethylformamide (2.0 ml), followed by stirring for an additional 45 minutes at 0° C. A mixture of 7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (4.9 g) and trimethylsilylacetamide (11 g) in methylene chloride (100 ml) was warmed to make a clear solution. The solution was cooled to -15° C. and added to the above obtained solution, followed by stirring for 30 minutes at 0° C. The reaction mixture was poured into a cold aqueous solution of sodium bicarbonate. The aqueous layer was separated and thereto was added ethyl acetate. The resulting mixture was adjusted to pH 2 with 10% hydrochloric acid, filtered to remove an insoluble material and then saturated with sodium chloride. The ethyl acetate layer was separated, dried over magnesium sulfate and evaporated. The residue was triturated with diethyl ether to give a crude product of the title compound (1.2 g). The crude material was dissolved in an aqueous solution of sodium bicarbonate, and reprecipitated with 10% hydrochloric acid. The precipitates were collected by filtration, washed with water and dried to give the title compound (0.35 g), mp. 185° to 190° C. (dec.).

Workup

  1. temperaturecooled to 0° C.
  2. stirringby stirring for an additional 45 minutes at 0° C
  3. temperaturewas warmed
  4. temperatureThe solution was cooled to -15° C.
  5. additionadded to the above obtained solution
  6. stirringby stirring for 30 minutes at 0° C
  7. customThe aqueous layer was separated
  8. additionwas added ethyl acetate
  9. filtrationfiltered
  10. customto remove an insoluble material
  11. customThe ethyl acetate layer was separated
  12. dry with materialdried over magnesium sulfate
  13. customevaporated
  14. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-50ce5b8267324a95b323746c54b79d33
Source dataset
uspto-grants-1984_05
Patent number
US04447429

Reaction notes

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