Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-propoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate

HRID 848336Notes

Reaction equation

HRID 848336 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH3:22])[C:15]([OH:17])=O)[N:13]=1)=[O:7].Cl.[NH2:24][CH:25]1[C:46](=[O:47])[N:27]2[C:28]([C:33]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([N+:43]([O-:45])=[O:44])=[CH:39][CH:38]=3)=[O:34])=[C:29]([Cl:32])[CH2:30][S:31][C@H:26]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:9][N+:13]([CH3:12])=[CH:29][Cl:32].[Cl-:3].[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH2:20][CH2:21][CH3:22])[C:15]([NH:24][CH:25]2[C:46](=[O:47])[N:27]3[C:28]([C:33]([O:35][CH2:36][C:37]4[CH:38]=[CH:39][C:40]([N+:43]([O-:45])=[O:44])=[CH:41][CH:42]=4)=[O:34])=[C:29]([Cl:32])[CH2:30][S:31][C@H:26]23)=[O:17])[N:13]=1)=[O:7]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 536876672-(2-Formamidothiazol-4-yl)-2-propoxyiminoacetic acidHCID 703621504-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317124674-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-propoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylateYield 170.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

The Vilsmeier reagent was prepared from N,N-dimethylformamide (0.4 g.) and phosphoryl chloride (0.86 g.) in a usual manner. After the reagent was suspended in ethyl acetate (10 ml.), 2-(2-formamidothiazol-4-yl)-2-n-propoxyiminoacetic acid (syn isomer, 1.3 g.) was added to the stirred suspension under ice cooling and stirred at the same temperature for 30 minutes. The solution was added to a solution of 4-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride (2.0 g.), trimethylsilylacetamide (5.2 g.) and ethyl acetate (40 ml.) at -25° C., and stirred at -20° to -10° C. for 1.5 hours. After adding water into the resultant solution, the solution was extracted with ethyl acetate (60 ml.). The aqueous layer was extracted with ethyl acetate (50 ml.). The extracts were combined together, washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, and dried over magnesium sulfate. The solution was concentrated in vacuo, and the residue was triturated with diethyl ether. The precipitates were collected by filtratation, washed and dried to give 4-nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-n-propoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate (syn isomer, 2.55 g.).

Workup

  1. stirringstirred at -20° to -10° C. for 1.5 hours
  2. extractionthe solution was extracted with ethyl acetate (60 ml.)
  3. extractionThe aqueous layer was extracted with ethyl acetate (50 ml.)
  4. washwashed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materiala saturated aqueous solution of sodium chloride in turn, and dried over magnesium sulfate
  6. concentrationThe solution was concentrated in vacuo
  7. customthe residue was triturated with diethyl ether
  8. customThe precipitates were collected by filtratation
  9. washwashed
  10. customdried

Sources & evidence

ORD record
ord-ffb0eae8606e4593a490612d94c042d4
Source dataset
uspto-grants-1981_10
Patent number
US04294960

Reaction notes

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