Acetamide, 2-(trimethylsilyl)- → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-ethoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

HRID 364559Notes

Reaction equation

HRID 364559 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH3:16])[C:10]([OH:12])=O)[N:8]=1)=[O:2].C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[NH2:37][CH:38]1[C:59](=[O:60])[N:40]2[C:41]([C:46]([O:48][CH2:49][C:50]3[CH:55]=[CH:54][C:53]([N+:56]([O-:58])=[O:57])=[CH:52][CH:51]=3)=[O:47])=[C:42]([OH:45])[CH2:43][S:44][C@H:39]12>C(OCC)(=O)C.O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH3:16])[C:10]([NH:37][CH:38]2[C:59](=[O:60])[N:40]3[C:41]([C:46]([O:48][CH2:49][C:50]4[CH:51]=[CH:52][C:53]([N+:56]([O-:58])=[O:57])=[CH:54][CH:55]=4)=[O:47])=[C:42]([OH:45])[CH2:43][S:44][C@H:39]23)=[O:12])[N:8]=1)=[O:2]

Participants

7

Reactant 4

HCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 544580772-(2-Formamidothiazol-4-yl)-2-ethoxyiminoacetic acidHCID 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

Product 1

HCID 1317124734-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-ethoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylateYield 77.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

N,N-Dimethylformamide (0.114 g.), phosphoryl chloride (0.240 g.) and ethyl acetate (0.5 ml.) were reacted in a conventional manner to give a Vilsmeier reagent. Ethyl acetate (5 ml.) and 2-(2-formamidothiazol-4-yl)-2-ethoxyiminoacetic acid (syn isomer, 0.35 g.) were added at the same temperature for 30 minutes to give the activated acid solution. On the other hand, trimethylsilylacetamide (1.31 g.) and bis(trimethylsilyl)acetamide (1.14 g.) were added to a suspension of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (0.50 g.) in ethyl acetate (7.5 ml.) and stirred at room temperature for an hour. To the solution was added the activated acid solution obtained above all at once at -10° C., and stirred at the same temperature for 30 minutes. Water (15 ml.) and ethyl acetate (15 ml.) were added to the resultant solution. The organic layer was separated, washed with a saturated aqueous solution of sodium bicarbonate (15 ml.) and water (10 ml.), dried over magnesium sulfate and 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-ethoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 0.634 g.).

Workup

  1. customto give the activated acid solution
  2. additionTo the solution was added the activated acid solution
  3. customobtained above all at once at -10° C.
  4. stirringstirred at the same temperature for 30 minutes
  5. customThe organic layer was separated
  6. washwashed with a saturated aqueous solution of sodium bicarbonate (15 ml.) and water (10 ml.)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-ca1f90cb626441529ddb6b7b8ecbdc89
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

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