Phosphorus oxychloride → HCID 178502766, compound

HRID 1381359Notes

Reaction equation

HRID 1381359 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:38](=[O:39])[N:22]2[C:23]([C:35]([OH:37])=[O:36])=[C:24]([CH:27]([S:29][C:30]3[NH:34][N:33]=[N:32][N:31]=3)[CH3:28])[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:38](=[O:39])[N:22]2[C:23]([C:35]([OH:37])=[O:36])=[C:24]([CH:27]([S:29][C:30]3[NH:31][N:32]=[N:33][N:34]=3)[CH3:28])[CH2:25][S:26][C@H:21]12)=[O:7]

Participants

8

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 533952072-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acidHCID 1784773817-Amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid

Product 1

HCID 178502766HCID 178502766, compoundYield 47.3%

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) (100 mg) and phosphorus oxychloride (306 mg) in methylene chloride (5 ml) was stirred for 30 minutes at ambient temperature. To the mixture was added N,N-dimethylformamide (0.2 ml) under cooling in an ice-bath, followed by stirring for 30 minutes. A mixture of 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (300 mg) and trimethylsilylacetamide (0.9 g) in methylene chloride (9 ml) was warmed to make a clear solution. The solution was cooled in an ice-bath 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, adjusted to pH 1 with 10% hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was triturated with diethyl ether to give a crude product of the title compound (120 mg). The crude material was dissolved in an aqueous solution of sodium bicarbonate and reprecipitated with diluted hydrochloric acid to give the pure title compound (60 mg), mp. 170° to 175° C. (dec.).

Workup

  1. temperatureunder cooling in an ice-bath
  2. stirringby stirring for 30 minutes
  3. temperaturewas warmed
  4. temperatureThe solution was cooled in an ice-bath
  5. additionadded to the above obtained solution
  6. stirringby stirring for 30 minutes at 0° C
  7. customThe aqueous layer was separated
  8. extractionextracted with ethyl acetate
  9. dry with materialThe extract was dried over anhydrous magnesium sulfate
  10. customevaporated to dryness
  11. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-1e4b7194b4f84ac1b39c28e08eb1c93d
Source dataset
uspto-grants-1986_04
Patent number
US04585872

Reaction notes

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