Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 1155174Notes

Reaction equation

HRID 1155174 reaction equation
P(Cl)(Cl)([Cl:3])=O.[CH:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O)([CH3:8])[CH3:7].[CH3:23][CH:24]1[CH:29]=[C:28]([C:30]([OH:32])=[O:31])[N:27]2[C:33](=[O:36])[CH:34]([NH2:35])[C@H:26]2[S:25]1.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH3:26][N+:27]([CH3:33])=[CH:28][Cl:3].[Cl-:3].[CH3:23][CH:24]1[CH:29]=[C:28]([C:30]([OH:32])=[O:31])[N:27]2[C:33](=[O:36])[CH:34]([NH:35][C:12](=[O:14])[C:11](=[N:10][O:9][CH:6]([CH3:7])[CH3:8])[C:15]3[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=3)[C@H:26]2[S:25]1

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128022512-Methyl-7-amino-3-cephem-4-carboxylic acidHCID 538092752-(2-Formamidothiazol-4-yl)-2-isopropoxyiminoacetic acidHCID 178460226HCID 178460226, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131712548HCID 131712548, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

The Vilsmeier reagent was prepared from dimethylformamide (0.44 g) and phosphorus oxychloride (0.92 g) in the conventional manner, and thereto was added ethyl acetate (20 ml). To the mixture was added 2-isopropoxyimino-2-(2-formylaminothiazol-4-yl)acetic acid (syn isomer), which can be represented as 2-isopropoxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetic acid (syn isomer), (1.29 g) under cooling at -5° to 0° C. with stirring and then stirring was continued for 20 minutes to give a clear solution. Thus obtained solution was added at a time to solution, which was prepared by warming a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (1.44 g) and trimethylsilylacetamide (4.6 g) in ethyl acetate (30 ml) at 40° C. followed by stirring for 30 minutes, under cooling at -20° to -15° C. with stirring. The resulting mixture was stirred for 1.5 hours at the same temperature and thereto was added water (20 ml). The mixture was stirred for 20 minutes at room temperature. The precipitates were collected by filtration, washed with a small amount of ethyl acetate, washed well with water and then dried to give 2-methyl-7-[2-isopropoxyimino-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), which can be represented as 2-methyl-7-[2-isopropoxyimino-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer), (1.8 g).

Workup

  1. temperatureunder cooling at -5° to 0° C.
  2. stirringstirring
  3. customto give a clear solution
  4. additionThus obtained solution was added at a time to solution, which
  5. customwas prepared
  6. temperatureby warming
  7. stirringby stirring for 30 minutes
  8. temperatureunder cooling at -20° to -15° C.
  9. stirringwith stirring
  10. stirringThe resulting mixture was stirred for 1.5 hours at the same temperature
  11. stirringThe mixture was stirred for 20 minutes at room temperature
  12. filtrationThe precipitates were collected by filtration
  13. washwashed with a small amount of ethyl acetate
  14. washwashed well with water
  15. customdried

Sources & evidence

ORD record
ord-6fbdbd76b8c94a1d8a537b5ec53050a0
Source dataset
uspto-grants-1981_11
Patent number
US04299829

Reaction notes

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