Phosphorus oxychloride → HCID 68121959, compound

HRID 621353Notes

Reaction equation

HRID 621353 reaction equation
C(NC1SC=C(C(=NOCC#C)C(O)=O)N=1)=O.P(Cl)(Cl)(Cl)=O.[ClH:23].N[CH:25]1[C:35](=[O:36])[N:27]2[C:28]([C:32]([OH:34])=[O:33])=[CH:29][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>C(OCC)(=O)C.O.CN(C)C=O>[Cl:23][C:29]1[CH2:30][S:31][C@@H:26]2[CH2:25][C:35](=[O:36])[N:27]2[C:28]=1[C:32]([OH:34])=[O:33]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 537194582-(2-Formamidothiazol-4-yl)-2-(propargyloxyimino)acetic acidHCID 70393944HCID 70393944, compound

Product 1

HCID 68121959HCID 68121959, compoundYield 80.8%

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 (400 mg.), phosphoryl chloride (850 mg.) and ethyl acetate (11.2 ml.) were treated in a conventional manner to give the activated acid solution. The activated acid solution was added to a solution of 7-amino-3-cephem-4-carboxylic acid hydrochloride (2 g.), trimethylsilylacetamide (6 g.) and bis(trimethylsilyl)acetamide (3 ml.) in ethyl acetate (40 ml.) at -15° C. all at once, and stirred at -5° to -10° C. for 1.5 hours. After adding water (30 ml.) to the resultant solution, the ethyl acetate layer was separated and extracted with a saturated aqueous solution of sodium bicarbonate. Ethyl acetate was added to the aqueous extract, adjusted to pH 2.0 with 10% hydrochloric acid. The ethyl acetate layer was separated, washed with water, dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo, and the residue was crystallized with a mixture of ethyl acetate and diisopropyl ether. The precipitates were collected by filtration and dried to give 7-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-chloro-3-cephem-4-carboxylic acid (syn isomer, 1.5 g.), yellow powder.

Workup

  1. customto give the activated acid solution
  2. customthe ethyl acetate layer was separated
  3. extractionextracted with a saturated aqueous solution of sodium bicarbonate
  4. additionEthyl acetate was added to the aqueous extract
  5. customThe ethyl acetate layer was separated
  6. washwashed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was crystallized with a mixture of ethyl acetate and diisopropyl ether
  11. filtrationThe precipitates were collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-36f0766a0bae476a944e1dc255cf02d0
Source dataset
uspto-grants-1989_04
Patent number
US04822888

Reaction notes

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