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

HRID 848313Notes

Reaction equation

HRID 848313 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 as 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-2d5e835d74c54d52baf1242700cf7f67
Source dataset
uspto-grants-1981_10
Patent number
US04294960

Reaction notes

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