Reaktion #63704

Reaktionsgleichung

2-[2,4-dichloro-5-(1-methylethoxy)phenyl]-1,2,4-triazine-3,5(2H,4H)-dione

Compound 51

2-[2,4-dichloro-5-(1-methylethoxy)phenyl]-1,2,4-triazine-3,5(2H,4H)-dione

sodium hydride

1-bromo-2-fluoroethane

potassium hydroxide

→

2-[2,4-dichloro-5-(1-methylethoxy)phenyl]-4-(2-fluoroethyl)-1,2,4-triazine-3,5(2H,4H)-dione

Ausbeute 36.8%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture was heated at 60°-70° C. for approximately 1.5 hours
2. 2
   TemperaturWhile maintaining the temperature at 60° C.
3. 3
   workup.ADDITIONAfter complete addition
4. 4
   Temperaturto cool to room temperature
5. 5
   workup.STIRRINGwas stirred for approximately 18 hours
6. 6
   SonstigeThe mixture was partitioned between dilute aqueous hydrochloric acid and ethyl acetate
7. 7
   TrocknenThe organic phase was dried over anhydrous magnesium sulfate
8. 8
   Filtrationfiltered
9. 9
   SonstigeEvaporation of the filtrate under reduced pressure
10. 10
    Sonstigeproduced an oil
11. 11
    Wascheneluting with ethyl acetate:n-heptane (1:1)
12. 12
    SonstigeEvaporation of the appropriate fractions
13. 13
    Sonstigeprovided a solid which
14. 14
    Sonstigewas recrystallized from ethyl acetate

Vorschrift

To a stirred mixture of 0.084 g (0.0035 mole) of sodium hydride in 20 mL of tetrahydrofuran was added a solution of 1.0 g (0.003 mole) of 2-[2,4-dichloro-5-(1-methylethoxy)phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (Compound 51, Example III, Step F) in 5 mL of tetrahydrofuran. The resulting mixture was stirred at room temperature for one hour. Tetrabutylammonium bromide (0.5 g, 0.002 mole) and potassium hydroxide (0.5 g, 0.009 mole) were added, and the mixture was heated at 60°-70° C. for approximately 1.5 hours. While maintaining the temperature at 60° C., a solution of 0.5 g (0.004 mole) of 1-bromo-2-fluoroethane in 5 mL of tetrahydrofuran was added. After complete addition, the mixture was allowed to cool to room temperature and was stirred for approximately 18 hours. The mixture was partitioned between dilute aqueous hydrochloric acid and ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and filtered. Evaporation of the filtrate under reduced pressure produced an oil. The oil was subjected to column chromatography on silica gel, eluting with ethyl acetate:n-heptane (1:1). Evaporation of the appropriate fractions provided a solid which was recrystallized from ethyl acetate:n-heptane to give 0.4 g of 2-[2,4-dichloro-5-(1-methylethoxy)phenyl]-4-(2-fluoroethyl)-1,2,4-triazine-3,5(2H,4H)-dione, Compound 26 in the tables.

Quelle