Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 1262749Notes

Reaction equation

HRID 1262749 reaction equation
P(Cl)(Cl)([Cl:3])=O.[Cl:6][CH2:7][C:8](=[O:20])[C:9](=[N:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C:10]([OH:12])=O.[CH3:21][N+:22]([CH3:25])=[CH:23][Cl:24].[Cl-].Cl.[NH2:28][CH:29]1[C:53](=[O:54])[N:31]2[C:32]([C:37]([O:39][CH:40]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[S:38])=[C:33]([CH3:36])[CH2:34][S:35][C@H:30]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:21][N+:22]([CH3:25])=[CH:23][Cl:24].[Cl-:3].[Cl:6][CH2:7][C:8](=[O:20])[C:9](=[N:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C:10]([NH:28][CH:29]1[C:53](=[O:54])[N:31]2[C:32]([C:37]([O:39][CH:40]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)=[S:38])=[C:33]([CH3:36])[CH2:34][S:35][C@H:30]12)=[O:12]

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 248204364-Chloro-2-methoxycarbonylmethoxyimino-3-oxobutyric acidHCID 131713528HCID 131713528, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131713527HCID 131713527, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (10.1 g) and dimethylformamide (4.8 g) in ethyl acetate (16 ml) in a usual manner. 4-Chloro-2-methoxycarbonylmethoxyimino-3-oxobutyric acid (syn isomer) (15.7 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (116 ml) under ice-cooling and the mixture was stirred at this temperature for 30 minutes to give an activated acid solution. To a solution of benzhydryl 7-amino-3-methylthio-3-cephem-4-carboxylate, hydrochloride (26.9 g) and trimethylsilylacetamide (42 g) in ethyl acetate (300 ml) was added the above activated acid solution at -20° C., and the mixture was stirred at -20° to 0° C. for one hour. To the reaction mixture was added water (200 ml) and the ethyl acetate layer was separated. The ethyl acetate layer was washed with saturated sodium bicarbonate solution and brine, and dried over magnesium sulfate. The solution was evaporated and the residue was triturated with ether to give benzhydryl 7-(4-chloro-2-methoxycarbonylmethoxyimino-3-oxobutyramido]-3-methylthio-3-cephem-4-carboxylate (syn isomer) (35.7 g).

Workup

  1. temperaturecooling
  2. customto give an activated acid solution
  3. stirringthe mixture was stirred at -20° to 0° C. for one hour
  4. customthe ethyl acetate layer was separated
  5. washThe ethyl acetate layer was washed with saturated sodium bicarbonate solution and brine
  6. dry with materialdried over magnesium sulfate
  7. customThe solution was evaporated
  8. customthe residue was triturated with ether

Sources & evidence

ORD record
ord-3770f85e34fb4d949dda59169189dca8
Source dataset
uspto-grants-1984_06
Patent number
US04452851

Reaction notes

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