Reaktion #522467

Reaktionsgleichung

phosphorus oxychloride

7-amino-2,3-dimethyl-3-cephem-4-carboxylic acid

trimethylsilylacetamide

2-{2-(2,2,2-Trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetic acid

Vilsmeier reagent

→

7-[2-{2-(2,2,2-trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetamido]-2,3-dimethyl-3-cephem-4-carboxylic acid

Ausbeute 81.1%

Lösungsmittel

ethyl acetate

dimethylformamide

water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto prepare the activated acid solution
2. 2
   workup.STIRRINGthe mixture was stirred at the same temperature for 40 minutes
3. 3
   Sonstigethe ethyl acetate layer was separated from the mixture
4. 4
   Waschenwashed with water
5. 5
   workup.ADDITIONWater (30 ml.) was added to the solution
6. 6
   Temperaturcooling
7. 7
   workup.STIRRINGAfter shaking the mixture
8. 8
   Sonstigethe aqueous layer was separated
9. 9
   workup.ADDITIONEthyl acetate (50 ml.) was added to the aqueous solution
10. 10
    workup.STIRRINGwith stirring
11. 11
    Sonstigethe ethyl acetate layer was separated
12. 12
    Waschenwashed with water
13. 13
    workup.ADDITIONa saturated aqueous solution of sodium chloride in turn, treated with activated charcoal
14. 14
    Trocknendried over magnesium sulfate
15. 15
    Einengenconcentrated under reduced pressure

Vorschrift

2-{2-(2,2,2-Trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetic acid (syn isomer, 0.65 g.) was added at 0° C. to Vilsmeier reagent which had been prepared from dimethylformamide and phosphorus oxychloride in ethyl acetate (10 ml.), and the mixture was stirred at the same temperature for 40 minutes to prepare the activated acid solution. The activated acid solution was added dropwise to a solution of 7-amino-2,3-dimethyl-3-cephem-4-carboxylic acid (0.5 g.) and trimethylsilylacetamide (1.73 g.) in ethyl acetate (30 ml.) at -20° C., and the mixture was stirred at the same temperature for 40 minutes. To the resultant mixture was added water (10 ml.), and the ethyl acetate layer was separated from the mixture and washed with water. Water (30 ml.) was added to the solution and the mixture was adjusted to pH 7.5 with sodium bicarbonate under ice-cooling. After shaking the mixture, the aqueous layer was separated. Ethyl acetate (50 ml.) was added to the aqueous solution, and the mixture was adjusted to pH 2 with dilute hydrochloric acid with stirring, and the ethyl acetate layer was separated, washed with water and a saturated aqueous solution of sodium chloride in turn, treated with activated charcoal, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was pulverized with diisopropyl ether to give 7-[2-{2-(2,2,2-trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetamido]-2,3-dimethyl-3-cephem-4-carboxylic acid (syn isomer, 0.9 g.).

Quelle