Reaktion #472754

Reaktionsgleichung

2-chloro-5-fluoropyridin-3-amine

butyl acrylate

water

ethyl acetate

→

butyl (2E)-3-(3-amino-5-fluoropyridin-2-yl)acrylate

Lösungsmittel

N,N-dimethylformamide

triethylamine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was cooled to 58° C.
2. 2
   workup.STIRRINGthe mixture was stirred at 110 to 120° C. for 40 minutes
3. 3
   TemperaturThe reaction mixture was cooled to 57° C.
4. 4
   workup.STIRRINGthe mixture was stirred at 110 to 120° C. for 3 hours
5. 5
   TemperaturThe reaction mixture was cooled to room temperature
6. 6
   FiltrationThe insoluble substance was filtered off
7. 7
   Sonstigethe organic layer of the filtrate was separated
8. 8
   Extraktionthe aqueous layer was extracted with ethyl acetate
9. 9
   Waschenthe resultant solution was washed sequentially with water
10. 10
    Trocknena saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate
11. 11
    workup.DISTILLATIONthe solvent was distilled off under reduced pressure
12. 12
    workup.ADDITIONCyclohexane and ethyl acetate were added to the resultant residue
13. 13
    Filtrationthe solid was filtered off

Vorschrift

To a solution of 150 g of 2-chloro-5-fluoropyridin-3-amine in 600 mL of N,N-dimethylformamide, 190 mL of butyl acrylate and 287 mL of triethylamine were added under a nitrogen flow, and the mixture was stirred at 110° C. for 2 hours. The reaction mixture was cooled to 58° C., thereto were added 13.1 g of bis(tri-tert-butylphosphine)palladium(0), and the mixture was stirred at 110 to 120° C. for 40 minutes. The reaction mixture was cooled to 57° C., 13.1 g of bis(tri-tert-butylphosphine)palladium(0) was added thereto, and the mixture was stirred at 110 to 120° C. for 3 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added thereto. The insoluble substance was filtered off, the organic layer of the filtrate was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed sequentially with water and a saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Cyclohexane and ethyl acetate were added to the resultant residue, and the solid was filtered off to obtain 200 g of butyl (2E)-3-(3-amino-5-fluoropyridin-2-yl)acrylate as a light brown solid.

Quelle