Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

HRID 435335

Reaction equation

HRID 435335 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.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[NH2:43][CH:44]1[C:65](=[O:66])[N:46]2[C:47]([C:52]([O:54][CH2:55][C:56]3[CH:61]=[CH:60][C:59]([N+:62]([O-:64])=[O:63])=[CH:58][CH:57]=3)=[O:53])=[C:48]([OH:51])[CH2:49][S:50][C@H:45]12>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:43][CH:44]2[C:65](=[O:66])[N:46]3[C:47]([C:52]([O:54][CH2:55][C:56]4[CH:57]=[CH:58][C:59]([N+:62]([O-:64])=[O:63])=[CH:60][CH:61]=4)=[O:53])=[C:48]([OH:51])[CH2:49][S:50][C@H:45]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 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

Product 1

HCID 1317130574-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylateYield 60.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetic acid (syn isomer, 0.506 g.), N,N-dimethylformamide (0.161 g.), phosphoryl chloride (0.337 g.) and ethyl acetate (7.9 ml.) were treated in a similar manner to that of Example 15-(1) to give the activated acid solution. On the other hand, trimethylsilylacetamide (1.85 g.) and bis(trimethylsilyl)acetamide (1.60 g.) were added to a suspension of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (0.703 g.) in ethyl acetate (10 ml.) and stirred at room temperature for an hour. To the solution was added the activated acid solution obtained above at -10° C. all at once, and stirred at the same temperature for an hour. Water (20 ml.) and ethyl acetate (20 ml.) were added to the solution. The organic layer was separated, washed with a saturated aqueous solution of sodium bicarbonate (8 ml.) and an aqueous solution of sodium chloride (15 ml.), and dried over magnesium sulfate. After the solution was concentrated in vacuo, the residue was pulverized with diethyl ether and the precipitates were collected by filtration to give 4-nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-propargyloxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 0.71 g.).

Workup

  1. customto give the activated acid solution
  2. additionTo the solution was added the activated acid solution
  3. customobtained above at -10° C. all at once, and
  4. stirringstirred at the same temperature for an hour
  5. customThe organic layer was separated
  6. washwashed with a saturated aqueous solution of sodium bicarbonate (8 ml.)
  7. dry with materialan aqueous solution of sodium chloride (15 ml.), and dried over magnesium sulfate
  8. concentrationAfter the solution was concentrated in vacuo
  9. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-a8e5e36111cd49a6b57085372c25ff08
Source dataset
uspto-grants-1983_08
Patent number
US04400379

Linked notes

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