Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 364511Notes

Reaction equation

HRID 364511 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[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:49](=[O:50])[N:31]2[C:32]([C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][C:43]([N+:46]([O-:48])=[O:47])=[CH:42][CH:41]=3)=[O:37])=[CH:33][CH2:34][S:35][C@H:30]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)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:49](=[O:50])[N:31]3[C:32]([C:36]([O:38][CH2:39][C:40]4[CH:41]=[CH:42][C:43]([N+:46]([O-:48])=[O:47])=[CH:44][CH:45]=4)=[O:37])=[CH:33][CH2:34][S:35][C@H:30]23)=[O:23])[N:19]=1)=[O:13]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 70362167p-Nitrobenzyl 7-amino-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 1317124414-Nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylateYield 49.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent prepared from dimethylformamide (0.43 g.) and phosphorus oxychloride (0.92 g.) was suspended in dry ethyl acetate (10 ml.). To the suspension was added 2-(2-formamido-4-thiazolyl)-2-methoxyimino acetic acid (syn isomer, 1.15 g.) under ice-cooling with stirring, and the mixture was stirred at the same temperature for 30 minutes to prepared the activated acid solution. On the other hand, p-nitrobenzyl 7-amino-3-cephem-4-carboxylate hydrochloride (1.79 g.) and trimethylsilylacetamide (5.0 g.) were dissolved in ethyl acetate (40 ml.). To the solution was added the activated acid solution at -20° C. all at once, and the mixture was stirred at the same temperature for 2.5 hours. Water (60 ml.) and ethyl acetate (200 ml.) were added to the resultant solution, and the ethyl acetate layer was separated, washed with 10% hydrochloric acid (60 ml.), a saturated aqueous solution of sodium bicarbonate (60 ml.) and an aqueous solution of sodium chloride (50 ml.) in turn, dried over magnesium sulfate, treated with activated charcoal, and then evaporated under reduced pressure. Diethyl ether was added to the residue, and the precipitates were collected by filtration to give p-nitrobenzyl 7-{2-(2-formamido-4-thiazolyl)-2-methoxyimino-acetamido}-3-cephem-4-carboxylate (syn isomer, 1.30 g.), m.p. 210° to 212° C. (dec.).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at the same temperature for 30 minutes
  3. customto prepared the activated acid solution
  4. additionTo the solution was added the activated acid solution at -20° C. all at once, and the mixture
  5. stirringwas stirred at the same temperature for 2.5 hours
  6. customthe ethyl acetate layer was separated
  7. washwashed with 10% hydrochloric acid (60 ml.)
  8. dry with materiala saturated aqueous solution of sodium bicarbonate (60 ml.) and an aqueous solution of sodium chloride (50 ml.) in turn, dried over magnesium sulfate
  9. additiontreated with activated charcoal
  10. customevaporated under reduced pressure
  11. additionDiethyl ether was added to the residue
  12. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-31962433205f4fec9643627046a5b0bb
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

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