7-Aminocephalosporanic acid → 8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1087420Notes

Reaction equation

HRID 1087420 reaction equation
CC(OC[C:6]1[CH2:15][S:14][C@@H:9]2[C@H:10](N)[C:11](=[O:12])[N:8]2[C:7]=1[C:16]([OH:18])=[O:17])=O>CN(C)C=O>[O:12]=[C:11]1[N:8]2[CH:9]([S:14][CH2:15][CH:6]=[C:7]2[C:16]([OH:18])=[O:17])[CH2:10]1

Participants

3

Reactant 1

HCID 4413287-Aminocephalosporanic acid

Product 1

HCID 190919938-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

In a second flask, 64 mg of (7R)-7-aminocephalosporanic acid and 124 mg of N,O-bis-(trimethylsilyl)acetamide in 1 ml of N,N-dimethylformamide were stirred at 20° C. for 20 minutes. A clear solution was obtained which was added at 0° C. to the solution in the first flask. The reaction mixture was stirred at 0° C. for 1 hour and at 20° C. for 2 hours. The precipitate was filtered off under suction and the filtrate was partitioned between 2% aqueous sodium hydrogen carbon solution and ethyl acetate. The aqueous phase was adjusted to pH 7 with 3N hydrochloric acid, concentrated in a vacuum to a volume of about 5 ml and the concentrated solution was chromatographed on MCI gel CHP2OP (Mitsubishi Chemical Industries Ltd.). Elution was carried out first with 1% aqueous acetic acid and then with mixtures of 1% aqueous acetic acid/methanol, using increasing amounts of methanol. By lyophilization of the product fractions, which were concentrated in a vacuum, there was obtained (6R,7R)-3-(acetoxymethyl)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl)]methoxy]imino]acetamido]-8-oxo-5-thia-1azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid as a white powder.

Workup

  1. customA clear solution was obtained which
  2. additionwas added at 0° C. to the solution in the first flask
  3. filtrationThe precipitate was filtered off under suction
  4. customthe filtrate was partitioned between 2% aqueous sodium hydrogen carbon solution and ethyl acetate
  5. concentrationconcentrated in a vacuum to a volume of about 5 ml
  6. customthe concentrated solution was chromatographed on MCI gel CHP2OP (Mitsubishi Chemical Industries Ltd.)
  7. washElution
  8. temperaturewith mixtures of 1% aqueous acetic acid/methanol, using increasing amounts of methanol
  9. concentrationBy lyophilization of the product fractions, which were concentrated in a vacuum

Sources & evidence

ORD record
ord-764569f9a09545ee87de86354996f058
Source dataset
uspto-grants-1991_07
Patent number
US05036064

Reaction notes

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