Phosphorus oxychloride → p-Nitrobenzyl 7-{2-(1,2,3-thiadiazol-4-yl)-2-methoxyiminoacetamido}-3-cephem-4-carboxylate

HRID 364527Notes

Reaction equation

HRID 364527 reaction equation
P(Cl)(Cl)([Cl:3])=O.[S:6]1[CH:10]=[C:9]([C:11](=[N:15][O:16][CH3:17])[C:12]([OH:14])=O)[N:8]=[N:7]1.[NH2:18][CH:19]1[C:39](=[O:40])[N:21]2[C:22]([C:26]([O:28][CH2:29][C:30]3[CH:35]=[CH:34][C:33]([N+:36]([O-:38])=[O:37])=[CH:32][CH:31]=3)=[O:27])=[CH:23][CH2:24][S:25][C@H:20]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>[CH3:20][N+:21]([CH3:39])=[CH:22][Cl:3].[Cl-:3].[S:6]1[CH:10]=[C:9]([C:11](=[N:15][O:16][CH3:17])[C:12]([NH:18][CH:19]2[C:39](=[O:40])[N:21]3[C:22]([C:26]([O:28][CH2:29][C:30]4[CH:31]=[CH:32][C:33]([N+:36]([O-:38])=[O:37])=[CH:34][CH:35]=4)=[O:27])=[CH:23][CH2:24][S:25][C@H:20]23)=[O:14])[N:8]=[N:7]1

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 543473402-Methoxyimino-2-(1,2,3-thiadiazol-4-yl)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131712449p-Nitrobenzyl 7-{2-(1,2,3-thiadiazol-4-yl)-2-methoxyiminoacetamido}-3-cephem-4-carboxylateYield 168.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

A solution of Vilsmeier reagent was prepared from dry dimethylformamide (0.39 g.), dry ethyl acetate (1.2 ml.) and phosphorus oxychloride (0.84 g.) in a usual manner. To the solution was added a solution of 2-(1,2,3-thiadiazol-4-yl)-2-methoxyiminoacetic acid (syn isomer, 0.93 g.) in ethyl acetate (10 ml.) at -15° C. to prepare the activated acid solution. On the other hand, a p-nitrobenzyl 7-amino-3-cephem-4-carboxylate (1.5 g.), trimethylsilylacetamide (4.6 g.) and bis(trimethylsilyl)acetamide (1 ml.) in dry ethyl acetate (50 ml.) was stirred at 45° C. for 5 hours to give a solution. To the solution was added all at once the activated acid solution obtained above at -10° C. with stirring, and the mixed solution was stirred at -5° C. for 1.5 hours. Water was added to the reaction mixture, and the insoluble product was separated by filtration, washed with ethyl acetate and water in turn, and then dried to give pale yellow powder of p-nitrobenzyl 7-{2-(1,2,3-thiadiazol-4-yl)-2-methoxyiminoacetamido}-3-cephem-4-carboxylate (syn isomer, 1.9 g.), m.p. 243° to 245° C. (dec.).

Workup

  1. customto prepare the activated acid solution
  2. customto give a solution
  3. additionTo the solution was added all at once the activated acid solution
  4. customobtained above at -10° C.
  5. stirringthe mixed solution was stirred at -5° C. for 1.5 hours
  6. customthe insoluble product was separated by filtration
  7. washwashed with ethyl acetate and water in turn
  8. customdried

Sources & evidence

ORD record
ord-6af656038e0d40cfa198b7a5a78d275f
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

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