Phosphorus oxychloride → p-Nitrobenzyl 7-{2(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate

HRID 1462731Notes

Reaction equation

HRID 1462731 reaction equation
P(Cl)(Cl)(Cl)=O.C[N+](C)=CCl.[Cl-].[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH3:26])[C:21]([OH:23])=O)[N:19]=1)=[O:13].Cl.[NH2:28][CH:29]1[C:50](=[O:51])[N:31]2[C:32]([C:37]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=[O:38])=[C:33]([Cl:36])[CH2:34][S:35][C@H:30]12>C(OCC)(=O)C.C[Si](CC(N)=O)(C)C.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH3:26])[C:21]([NH:28][CH:29]2[C:50](=[O:51])[N:31]3[C:32]([C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][C:44]([N+:47]([O-:49])=[O:48])=[CH:45][CH:46]=4)=[O:38])=[C:33]([Cl:36])[CH2:34][S:35][C@H:30]23)=[O:23])[N:19]=1)=[O:13]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chloride2×HCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 703621504-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 131712431p-Nitrobenzyl 7-{2(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylateYield 51.8%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×HCID 357676Acetamide, 2-(trimethylsilyl)-Solvent

Procedure

N,N-Dimethylformamide (0.16 g.) and phosphorous oxychloride (0.34 g.) were mixed to prepare Vilsmeier reagent in a usual manner, and the resultant Vilsmeier reagent was suspended in dry ethyl acetate. To the suspension was added 2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetic acid (syn isomer, 0.46 g.) under ice-cooling with stirring, and then the solution was stirred at the same temperature for 30 minutes to prepare the activated acid solution. p-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride (0.81 g.) was dissolved in a solution of trimethylsilylacetamide (2.10 g.) in ethyl acetate (200 ml.). To the solution was added the activated acid solution obtained above all at once at -20° C., and the solution was stirred at -20°~-5° C. for 1.5 hours. After water and ethyl acetate (100 ml.) were added to the resultant solution at -20° C. the insoluble product was separated by filtration, washed with water and acetone in turn and then dried to give p-nitrobenzyl 7-{2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido}-3-chloro-3-cephem-4-carboxylate (syn isomer, 0.6 g.).

Workup

  1. temperaturecooling
  2. stirringthe solution was stirred at the same temperature for 30 minutes
  3. customto prepare the activated acid solution
  4. additionTo the solution was added the activated acid solution
  5. customobtained above all at once at -20° C.
  6. stirringthe solution was stirred at -20°~-5° C. for 1.5 hours
  7. customwas separated by filtration
  8. washwashed with water and acetone in turn
  9. customdried

Sources & evidence

ORD record
ord-da796b0db1cd4d7d897fe23cc699a572
Source dataset
uspto-grants-1984_07
Patent number
US04460583

Reaction notes

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