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

HRID 364502Notes

Reaction equation

HRID 364502 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.). After ethyl acetate was removed from the above filtrate, the aqueous layer was extracted with ethyl acetate (50 ml.) twice. The ethyl acetate layer and the extract were combined together, washed with 10% hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn and then dried over magnesium sulfate. After removing ethyl acetate from the solution, diethyl ether was added to the residue. The insoluble product was collected by filtration to give the same object compound (0.25 g.), m.p. 226° to 228° C. (dec.), Total yield 0.85 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. customthe insoluble product was separated by filtration
  8. washwashed with water and acetone in turn
  9. customdried

Sources & evidence

ORD record
ord-4f78ba841a1942c1b2d4aef51e778ff1
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

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