Sodium Carbonate → 7-[2-(2-Formamidothiazol-4-yl)-2-(3-isoxazolylmethoxyimino)acetamido]-3-cephem-4-carboxylic acid

HRID 894795Notes

Reaction equation

HRID 894795 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][C:21]2[CH:25]=[CH:24][O:23][N:22]=2)[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:26][CH:27]1[C:37](=[O:38])[N:29]2[C:30]([C:34]([OH:36])=[O:35])=[CH:31][CH2:32][S:33][C@H:28]12.C(=O)([O-])[O-].[Na+].[Na+]>O.CC(C)=O.O1CCCC1.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][C:21]2[CH:25]=[CH:24][O:23][N:22]=2)[C:15]([NH:26][CH:27]2[C:37](=[O:38])[N:29]3[C:30]([C:34]([OH:36])=[O:35])=[CH:31][CH2:32][S:33][C@H:28]23)=[O:17])[N:13]=1)=[O:7]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 537376352-(2-Formamidothiazol-4-yl)-2-[(3-isoxazolyl)methoxyimino]acetic acid

Product 1

HCID 1317123347-[2-(2-Formamidothiazol-4-yl)-2-(3-isoxazolylmethoxyimino)acetamido]-3-cephem-4-carboxylic acidYield 77.4%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Phosphoryl chloride (1.02 g.), 2-(2-formamidothiazol-4-yl)-2-(3-isoxazolylmethoxyimino)-acetic acid (syn isomer, 1.0 g.), N,N-dimethylformamide (0.448 g.) and tetrahydrofuran (10 ml.) were treated in a similar manner to that of Example 5-(1) to give an activated acid solution. On the other hand, a mixture of 7-amino-3-cephem-4-carboxylic acid (0.91 g.), tetrahydrofuran (10 ml.) acetone (5 ml.) and water (5 ml.) was adjusted to pH 7:5 with 20% aqueous sodium carbonate at 0° to -5° C. The activated acid solution was added dropwise to the above solution at 0° to -5° C. while keeping at pH 7.5 to 8.0. The mixture was treated in a similar manner to that of Example 5-(1) to give 7-[2-(2-formamidothiazol-4-yl)-2-(3-isoxazolylmethoxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.25 g.)

Workup

  1. customto give an activated acid solution
  2. customat 0° to -5° C
  3. additionThe activated acid solution was added dropwise to the above solution at 0° to -5° C.
  4. additionThe mixture was treated in a similar manner to that of Example 5-(1)

Sources & evidence

ORD record
ord-cbc865fda0704a6f8a1813dcdeb3e466
Source dataset
uspto-grants-1981_08
Patent number
US04284631

Reaction notes

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