Phosphorus oxychloride → 7-[2-hydroxyimino-2-(3-hydroxyphenyl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 648408Notes

Reaction equation

HRID 648408 reaction equation
P(Cl)(Cl)([Cl:3])=O.Cl[CH:7]([Cl:23])C([O:10][N:11]=[C:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=1)[C:13]([OH:15])=O)=O.[NH2:24][CH:25]1[C:46](=[O:47])[N:27]2[C:28]([C:43]([OH:45])=[O:44])=[C:29]([CH2:32][S:33][C:34]3[N:38]([CH2:39][C:40]([OH:42])=[O:41])[N:37]=[N:36][N:35]=3)[CH2:30][S:31][C@H:26]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CC(C)=O.CN(C)C=O>[CH3:26][N+:27]([CH3:28])=[CH:7][Cl:23].[Cl-:3].[OH:10][N:11]=[C:12]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=1)[C:13]([NH:24][CH:25]1[C:46](=[O:47])[N:27]2[C:28]([C:43]([OH:45])=[O:44])=[C:29]([CH2:32][S:33][C:34]3[N:38]([CH2:39][C:40]([OH:42])=[O:41])[N:37]=[N:36][N:35]=3)[CH2:30][S:31][C@H:26]12)=[O:15]

Participants

10

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 127691497-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 541128092-Dichloroacetoxyimino-2-(3-hydroxyphenyl)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317124047-[2-hydroxyimino-2-(3-hydroxyphenyl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 132.9%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent4×

Conditions

Temperature
-10 °C

Procedure

The Vilsmeier reagent was prepared by conventional method from dimethylformamide (1.16 g.), phosphorus oxychloride (2.44 g.) and ethyl acetate (6 ml.). Ethyl acetate (10 ml.) was added thereto, and then a solution of 2-dichloroacetoxyimino-2-(3-hydroxyphenyl)acetic acid (syn isomer) (4.03 g.) in ethyl acetate (28 ml.) was added thereto with stirring at -10° C., after which the resulting mixture was stirred for 30 minutes at the same temperature to give a solution. On the other hand, a suspension of 7-amino-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (4.30 g.) in water (25 ml.) was dissolved by adding a saturated aqueous solution of sodium bicarbonate and acetone (50 ml.) was added thereto to adjust the pH of the solution at 7.5. To this solution was added dropwise with stirring at -10° C. the ethyl acetate solution obtained above, and then the resulting mixture was stirred for 1 hour at the same temperature, during which the pH of the mixture was kept at 6.5 to 7.0. The reaction mixture was adjusted to pH5.5 and washed with ethyl acetate (60 ml.). The aqueous layer was adjusted to pH2.0 and extracted with ethyl acetate (400 ml.). The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated. The residue was pulverized with diethyl ether and the powder was collected by filtration to give 7-[2-hydroxyimino-2-(3-hydroxyphenyl)acetamido]-3-(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (4.11 g.).

Workup

  1. stirringafter which the resulting mixture was stirred for 30 minutes at the same temperature
  2. customto give a solution
  3. dissolutionwas dissolved
  4. additionwas added
  5. additionTo this solution was added dropwise
  6. customobtained above, and then the resulting mixture
  7. stirringwas stirred for 1 hour at the same temperature, during which the pH of the mixture
  8. washwashed with ethyl acetate (60 ml.)
  9. extractionextracted with ethyl acetate (400 ml.)
  10. washThe extract was washed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated
  13. filtrationthe powder was collected by filtration

Sources & evidence

ORD record
ord-566cfab85a0240e0b8bfd0c61bf24d8c
Source dataset
uspto-grants-1983_10
Patent number
US04411898

Reaction notes

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