Phosphorus oxychloride → HCID 178502765, compound

HRID 2286999Notes

Reaction equation

HRID 2286999 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:17]=[C:16]([NH:18][CH:19]=[O:20])[S:15][N:14]=1)[C:10]([OH:12])=O.[NH2:21][CH:22]1[C:40](=[O:41])[N:24]2[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH:29]([S:31][C:32]3[NH:36][N:35]=[N:34][N:33]=3)[CH3:30])[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C)C=O>[CH3:6][O:7][N:8]=[C:9]([C:13]1[N:17]=[C:16]([NH:18][CH:19]=[O:20])[S:15][N:14]=1)[C:10]([NH:21][CH:22]1[C:40](=[O:41])[N:24]2[C:25]([C:37]([OH:39])=[O:38])=[C:26]([CH:29]([S:31][C:32]3[NH:33][N:34]=[N:35][N:36]=3)[CH3:30])[CH2:27][S:28][C@H:23]12)=[O:12]

Participants

8

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 544280122-Methoxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acidHCID 1784773817-Amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid

Product 1

HCID 178502765HCID 178502765, compoundYield 106.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of N,N-dimethylformamide (6 ml) and phosphorus oxychloride (918 mg) was stirred for 30 minutes at ambient temperature. To the mixture were added methylene chloride (6 ml) and 2-methoxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid (syn isomer) (1.1 g) at -15° to -10° C., followed by stirring for 30 minutes at the same temperature. A mixture of 7-amino-3-(1-methyl-1H-tetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid (1.97 g) and trimethylsilylacetamide (6 g) in methylene chloride (60 ml) was warmed to make a clear solution. The solution was cooled to -15° C. and added to the above obtained solution. The reaction mixture was stirred for an hour at 0° C. and poured into a cold aqueous solution of sodium bicarbonate. The aqueous layer was separated, adjusted to pH 2 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 (2.75 g). The crude material was dissolved in an aqueous solution of sodium bicarbonate and reprecipitated with diluted hydrochloric acid to give the pure title compound (1.5 g), mp. 170° to 175° C. (dec.).

Workup

  1. stirringby stirring for 30 minutes at the same temperature
  2. temperaturewas warmed
  3. temperatureThe solution was cooled to -15° C.
  4. additionadded to the above obtained solution
  5. stirringThe reaction mixture was stirred for an hour at 0° C.
  6. customThe aqueous layer was separated
  7. extractionextracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous magnesium sulfate
  9. customevaporated to dryness
  10. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-0eae0613bc524ff0996392876f4fd618
Source dataset
uspto-grants-1981_05
Patent number
US04268509

Reaction notes

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