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

HRID 848378

Reaction equation

HRID 848378 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:36](=[O:37])[N:27]2[C:28]([C:33]([OH:35])=[O:34])=[C:29]([Cl:32])[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>[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:36](=[O:37])[N:27]3[C:28]([C:33]([OH:35])=[O:34])=[C:29]([Cl:32])[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 703622557-Amino-3-chloro-3-cephem-4-carboxylic acid hydrochloride

Product 1

HCID 1317125027-[2-(2-Formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-chloro-3-cephem-4-carboxylic acidYield 63.7%

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-chloro-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-(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-3387b759882c46c1866867ab591b8549
Source dataset
uspto-grants-1981_10
Patent number
US04294960

Linked notes

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