Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 894808Notes

Reaction equation

HRID 894808 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][C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[C:23]([OH:28])[CH:22]=2)[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:29][N+:30]([CH3:33])=[CH:31][Cl:32].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:43][CH:44]1[C:54](=[O:55])[N:46]2[C:47]([C:51]([OH:53])=[O:52])=[CH:48][CH2:49][S:50][C@H:45]12>C(OCC)(=O)C.O.CN(C)C=O>[CH3:29][N+:30]([CH3:33])=[CH:31][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][C:21]2[CH:26]=[CH:25][C:24]([Br:27])=[C:23]([OH:28])[CH:22]=2)[C:15]([NH:43][CH:44]2[C:54](=[O:55])[N:46]3[C:47]([C:51]([OH:53])=[O:52])=[CH:48][CH2:49][S:50][C@H:45]23)=[O:17])[N:13]=1)=[O:7]

Participants

10

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 540633902-(2-Formamidothiazol-4-yl)-2-(4-bromo-3-hydroxybenzyloxyimino)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 131712351HCID 131712351, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from N,N-dimethylformamide (0.44 g.) and phosphoryl chloride (0.92 g.) in an usual manner. 2-(2-Formamidothiazol4-yl)-2-(4-bromo-3-hydroxybenzyloxyimino)acetic acid (syn isomer, 2.0 g.) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (18 ml.) under ice-cooling, and stirred at the same temperature for 30 minutes to give a solution [hereinafter referred to solution A]. Trimethylsilylacetamide (3.9 g.) was added to a stirred suspension of 7-amino-3-cephem-4-carboxylic acid (1.0 g.) in ethyl acetate (10 ml.) and the mixture was stirred at 40° C. for 30 minutes. To the solution was added the solution A all at once at -30° C., and stirred at -10° to -20° C. for an hour. Water (100 ml.) and ethyl acetate (100 ml.) were added to the resultant mixture at -10° C. After separating the organic layer, water (100 ml.) was added to the organic layer and adjusted to pH 7.0 with a sodium bicarbonate saturated solution. The aqueous layer was separated, and ethyl acetate was added thereto. The mixture was adjusted to pH 3.0 with 10% hydrochloric acid under ice-cooling. The organic layer was separated, washed with a sodium chloride saturated solution and dried over magnesium sulfate. The solution was concentrated in vacuo to give 7-[2-(2-formamidothiazol-4-yl)-2-(4-bromo-3-hydroxybenzyloxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 2.0 g.).

Workup

  1. temperaturecooling
  2. customto give a solution [
  3. stirringthe mixture was stirred at 40° C. for 30 minutes
  4. stirringstirred at -10° to -20° C. for an hour
  5. customAfter separating the organic layer, water (100 ml.)
  6. additionwas added to the organic layer and adjusted to pH 7.0 with a sodium bicarbonate saturated solution
  7. customThe aqueous layer was separated
  8. additionethyl acetate was added
  9. temperaturecooling
  10. customThe organic layer was separated
  11. washwashed with a sodium chloride saturated solution
  12. dry with materialdried over magnesium sulfate
  13. concentrationThe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-47f6cd90f8684638baa04d6437034784
Source dataset
uspto-grants-1981_08
Patent number
US04284631

Reaction notes

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