Phosphorus oxychloride → Chloro-N,N-dimethylformiminium chloride

HRID 894806Notes

Reaction equation

HRID 894806 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][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:45][CH:46]1[C:56](=[O:57])[N:48]2[C:49]([C:53]([OH:55])=[O:54])=[CH:50][CH2:51][S:52][C@H:47]12>C(OCC)(=O)C.O.CN(C)C=O>[CH3:31][N+:32]([CH3:35])=[CH:33][Cl:34].[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][CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:15]([NH:45][CH:46]2[C:56](=[O:57])[N:48]3[C:49]([C:53]([OH:55])=[O:54])=[CH:50][CH2:51][S:52][C@H:47]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 540266432-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317123497-[2-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from N,N-dimethylformamide (0.6 g.) and phosphoryl chloride (1.2 g.) in an usual manner. 2-(2-Formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetic acid (syn isomer, 2.6 g.) was added to a stirred suspension of the Vilsmeier reagent in ethyl acetate (30 ml.) under ice-cooling and stirred at the same temperature for 30 minutes [hereinafter referred to solution A]. Trimethylsilylacetamide (5.5 g.) was added to a stirred suspension of 7-amino-3-cephem-4-carboxylic acid (1.4 g.) in ethyl acetate (20 ml.), and the mixture was stirred at 40° C. for 30 minutes. The solution A was added to the solution at -10° to -30° C. and stirred at the same temperature for an hour. Water and ethyl acetate (100 ml.) were added to the reaction mixture at -10° C. and the ethyl acetate layer was separated. Water was added to the ethyl acetate layer, and adjusted to pH 7.5 with a sodium bicarbonate saturated aqueous solution. The aqueous solution was separated and ethyl acetate was added thereto. The mixture was adjusted to pH 2.8 with 10% hydrochloric acid under ice-cooling. The ethyl acetate layer was separated, washed with a sodium chloride saturated aqueous solution and dried over magnesium sulfate. The solution was concentrated in vacuo, and the residue was pulverized with diisopropyl ether to give 7-[2-(2-formamidothiazol-4-yl)-2-(3-tert-butoxycarbonylaminopropoxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 2.2 g.)

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred at 40° C. for 30 minutes
  3. stirringstirred at the same temperature for an hour
  4. customthe ethyl acetate layer was separated
  5. additionWater was added to the ethyl acetate layer
  6. customThe aqueous solution was separated
  7. additionethyl acetate was added
  8. temperaturecooling
  9. customThe ethyl acetate layer was separated
  10. washwashed with a sodium chloride saturated aqueous solution
  11. dry with materialdried over magnesium sulfate
  12. concentrationThe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-c51f331ecfba4bfdadfd82dd816a80a7
Source dataset
uspto-grants-1981_08
Patent number
US04284631

Reaction notes

Loading…