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

HRID 1905254Notes

Reaction equation

HRID 1905254 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][CH3:17])[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][CH2:16][CH3:17])[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 536876672-(2-Formamidothiazol-4-yl)-2-propoxyiminoacetic acidHCID 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

Product 1

HCID 1317124714-Nitrobenzyl 7-[(2-formamidothiazol-4-yl)-2-propoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylateYield 63.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

2-(2-Formamidothiazol-4-yl)-2-propoxyiminoacetic acid (syn isomer, 0.515 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. To the resultant solution were added water (20 ml.) and ethyl acetate (20 ml.). The organic layer was separated, washed with a saturated aqueous solution of sodium bicarbonate (8 ml.) and water (14 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-propoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 0.75 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.) and water (14 ml.)
  7. dry with materialdried over magnesium sulfate
  8. concentrationAfter the solution was concentrated in vacuo
  9. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-2ac0825c3b8d4a449275d14adaec95f4
Source dataset
uspto-grants-1989_06
Patent number
US04841062

Reaction notes

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