Hydrochloric Acid → Chloro-N,N-dimethylformiminium chloride

HRID 648840Notes

Reaction equation

HRID 648840 reaction equation
P(Cl)(Cl)([Cl:3])=O.[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[CH:22][S:23][CH:24]=1)[C:17]([OH:19])=O)=[O:12])([CH3:9])([CH3:8])[CH3:7].[CH3:25][N+:26]([CH3:29])=[CH:27][Cl:28].[Cl-].C[Si](CC(N)=O)(C)C.[NH2:39][CH:40]1[C:50](=[O:51])[N:42]2[C:43]([C:47]([OH:49])=[O:48])=[CH:44][CH2:45][S:46][C@H:41]12.C(=O)([O-])[O-].[K+].[K+].Cl>C(OCC)(=O)C.O1CCCC1.O.CN(C)C=O>[CH3:25][N+:26]([CH3:29])=[CH:27][Cl:28].[Cl-:3].[C:6]([O:10][C:11]([CH2:13][O:14][N:15]=[C:16]([C:20]1[N:21]=[CH:22][S:23][CH:24]=1)[C:17]([NH:39][CH:40]1[C:50](=[O:51])[N:42]2[C:43]([C:47]([OH:49])=[O:48])=[CH:44][CH2:45][S:46][C@H:41]12)=[O:19])=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 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 544727372-t-Butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317142047-[2-t-Butoxycarbonylmethoxyimino2-(4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Vilsmeier reagent was prepared from phosphorus oxychloride (0.76 g) and N,N-dimethylformamide (0.36 g) in ethyl acetate (1.44 ml) in a usual manner. 2-t-Butoxycarbonylmethoxyimino-2-(4-thiazolyl)acetic acid (syn isomer) (1.2 g) was added to the stirred suspension of Vilsmeier reagent in ethyl acetate (200 ml) under ice-cooling and the mixture was stirred for 20 minutes at the same temperature to prepare an activated acid solution. Trimethylsilylacetamide (3.5 g) was added to the stirred suspension of 7-amino-3-cephem-4-carboxylic acid (0.76 g) in tetrahydrofuran (15 ml) and the mixture was stirred for 20 minutes at 35° to 40° C. To the solution was added the above activated acid solution at -10° C. and the mixture was stirred for 30 minutes at the same temperature. Water was added to the reaction mixture and the separated organic layer was added to water and the mixture was adjusted to pH 7.5 with saturated aqueous solution of potassium carbonate. The separated aqueous layer was adjusted to pH 2.0 with 10% hydrochloric acid and extracted with ethyl acetate. The extracted layer was washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate and evaporated to give 7-[2-t-butoxycarbonylmethoxyimino2-(4-thiazolyl)acetamido]-3-cephem-4-carboxylic acid (syn isomer) (1.4 g).

Workup

  1. temperaturecooling
  2. customto prepare an activated acid solution
  3. stirringthe mixture was stirred for 20 minutes at 35° to 40° C
  4. additionTo the solution was added the above activated acid solution at -10° C.
  5. stirringthe mixture was stirred for 30 minutes at the same temperature
  6. extractionextracted with ethyl acetate
  7. washThe extracted layer was washed with saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. customevaporated

Sources & evidence

ORD record
ord-2396352525c04388944f72c6df1c1029
Source dataset
uspto-grants-1988_04
Patent number
US04736039

Reaction notes

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