Phosphorus oxychloride → HCID 131712240, compound

HRID 2287002Notes

Reaction equation

HRID 2287002 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:31](=[O:32])[N:22]2[C:23]([C:28]([OH:30])=[O:29])=[CH:24][CH:25]([CH3:27])[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:31](=[O:32])[N:22]2[C:23]([C:28]([OH:30])=[O:29])=[CH:24][CH:25]([CH3:27])[S:26][C@H:21]12)=[O:7]

Participants

8

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 128022512-Methyl-7-amino-3-cephem-4-carboxylic acidHCID 533952072-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid

Product 1

HCID 131712240HCID 131712240, compoundYield 92.3%

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) (1.21 g) and phosphorus oxychloride (3.67 g) in methylene chloride (30 ml) was stirred for two hours at ambient temperature, cooled to 0° C. and thereto was added N,N-dimethylformamide (2.4 ml), followed by stirring for an additional 45 minutes at 0° C. A mixture of 7-amino-2-methyl-3-cephem-4-carboxylic acid (3.0 g) and trimethylsilylacetamide (10 g) in methylene chloride (50 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 and the ethyl acetate layer was separated, dried over anhydrous magnesium sulfate and then evaporated. The residue was triturated with diethyl ether to give a crude product of the title compound (2.2 g). The crude material was dissolved in an aqueous solution of sodium bicarbonate, adjusted to pH 2 with 10% hydrochloric acid. The precipitates were collected by filtration, washed with ice-water and dried to give the title compound (1.6 g), mp. 175° to 180° 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. customthe ethyl acetate layer was separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated
  12. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-d337e03a06c94871acbeb39ba37adc75
Source dataset
uspto-grants-1981_05
Patent number
US04268509

Reaction notes

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