Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acid

HRID 435378Notes

Reaction equation

HRID 435378 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]#[CH:17])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.Cl.[NH2:24][CH:25]1[C:37](=[O:38])[N:27]2[C:28]([C:34]([OH:36])=[O:35])=[C:29]([O:32][CH3:33])[CH2:30][S:31][C@H:26]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>O.C(OCC)(=O)C.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][C:16]#[CH:17])[C:10]([NH:24][CH:25]2[C:37](=[O:38])[N:27]3[C:28]([C:34]([OH:36])=[O:35])=[C:29]([O:32][CH3:33])[CH2:30][S:31][C@H:26]23)=[O:12])[N:8]=1)=[O:2]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 537194582-(2-Formamidothiazol-4-yl)-2-(propargyloxyimino)acetic acidHCID 703620437-Amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride

Product 1

HCID 1317125017-[2-(2-Formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acidYield 43.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

2-(2-Formamidothiazol-4-yl)-2-propargyloxyiminoacetic acid (syn isomer, 1.27 g.), N,N-dimethylformamide (402 mg.), phosphoryl chloride (843 mg.) and ethyl acetate (11.2 ml.) were treated in a conventional manner to prepare an activated acid solution. On the other hand, a mixture of 7-amino-3-methoxy-3-cephem-4-carboxylic acid hydrochloride (1.33 g.), trimethylsilylacetamide (4 g.), bis(trimethylsilyl)acetamide (2 ml.) and ethyl acetate (20 ml.) was stirred at 40° to 45° C. for an hour. To the solution was added the activated acid solution obtained above all at once at -15° C., and then stirred at -5° to -10° C. for 1.5 hours. Water (30 ml.) was added to the resultant solution, filtered and the organic layer was separated. The insoluble substance filtered out was dissolved in a saturated aqueous solution of sodium bicarbonate, and the solution was added to the organic layer. The solution was adjusted to pH 7.5 and the aqueous solution was separated, and then extracted with ethyl acetate at pH 2.0. The extract was washed with water, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-methoxy-3-cephem-4-carboxylic acid (syn isomer, 1.0 g.), yellow powder.

Workup

  1. customto prepare an activated acid solution
  2. additionTo the solution was added the activated acid solution
  3. customobtained above all at once at -15° C.
  4. stirringstirred at -5° to -10° C. for 1.5 hours
  5. filtrationfiltered
  6. customthe organic layer was separated
  7. filtrationThe insoluble substance filtered out
  8. dissolutionwas dissolved in a saturated aqueous solution of sodium bicarbonate
  9. additionthe solution was added to the organic layer
  10. customthe aqueous solution was separated
  11. extractionextracted with ethyl acetate at pH 2.0
  12. washThe extract was washed with water
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f761bf2df98b41c29a52301c4a5a1ffc
Source dataset
uspto-grants-1983_08
Patent number
US04400379

Reaction notes

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