Water → Chloro-N,N-dimethylformiminium chloride

HRID 848350Notes

Reaction equation

HRID 848350 reaction equation
P(Cl)(Cl)([Cl:3])=O.[F:6][C:7]([F:16])([F:15])[CH2:8][O:9][N:10]=[CH:11][C:12]([OH:14])=O.[NH2:17][CH:18]1[C:28](=[O:29])[N:20]2[C:21]([C:25]([OH:27])=[O:26])=[CH:22][CH2:23][S:24][C@H:19]12.C[Si]([CH2:34][C:35]([NH2:37])=O)(C)C.[OH2:38]>C(OCC)(=O)C.CN(C)C=O>[CH3:19][N+:20]([CH3:28])=[CH:21][Cl:3].[Cl-:3].[CH:21]([NH:20][C:19]1[S:24][CH:34]=[C:35]([C:11](=[N:10][O:9][CH2:8][C:7]([F:6])([F:16])[F:15])[C:12]([NH:17][CH:18]2[C:28](=[O:29])[N:20]3[C:21]([C:25]([OH:27])=[O:26])=[CH:22][CH2:23][S:24][C@H:19]23)=[O:14])[N:37]=1)=[O:38]

Participants

9

Reactant 5

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 85578067HCID 85578067, compound

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317124807-[2-(2-Formamidothiazol-4-yl)-2-(2,2,2-trifluoroethoxyimino)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent4×

Procedure

The Vilsmeier reagent was prepared from N,N-dimethylformamide (0.32 g.) and phosphoryl chloride (0.67 g.) in a conventional manner. After the reagent was suspended in ethyl acetate (10 ml.), 2-(2-formamidothiazol-4-yl)-2-(2,2,2-trifluoroethoxyiminoacetic acid (syn isomer, 1.2 g.) was added to the stirred suspension under ice cooling and stirred at the same temperature for 30 minutes. The solution was added to a solution of 7-amino-3-cephem-4-carboxylic acid (0.8 g.), and trimethylsilylacetamide (4.2 g.) in ethyl acetate (20 ml.) at -25° C., and stirred at -20° to -10° C. for an hour. Water and ethyl acetate were added to the resultant solution, and ethyl acetate layer was separated. The aqueous layer was extracted again with ethyl acetate. Water was added to the combined extract and adjusted to pH 7.5 with a saturated aqueous solution of sodium bicarbonate, and then the aqueous layer was separated. Ethyl acetate was added to the aqueous layer, adjusted to pH 1.5 with hydrochloric acid and the ethyl acetate layer was separated. The aqueous layer was extracted again with ethyl acetate. The extracts were combined, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After concentrating the solution in vacuo, the residue was triturated with diethyl ether, and the precipitates were collected by filtration and dried to give 7-[2-(2-formamidothiazol-4-yl)-2-(2,2,2-trifluoroethoxyimino)acetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.55 g.).

Workup

  1. stirringstirred at -20° to -10° C. for an hour
  2. customwas separated
  3. extractionThe aqueous layer was extracted again with ethyl acetate
  4. additionWater was added to the
  5. extractioncombined extract
  6. customthe aqueous layer was separated
  7. additionEthyl acetate was added to the aqueous layer
  8. customthe ethyl acetate layer was separated
  9. extractionThe aqueous layer was extracted again with ethyl acetate
  10. washwashed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over magnesium sulfate
  12. concentrationAfter concentrating the solution in vacuo
  13. customthe residue was triturated with diethyl ether
  14. filtrationthe precipitates were collected by filtration
  15. customdried

Sources & evidence

ORD record
ord-4294a7f2dc0f428380be565751e734c1
Source dataset
uspto-grants-1981_10
Patent number
US04294960

Reaction notes

Loading…