Реакция #63704

Уравнение реакции

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

Выход 36.8%

Растворители

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Температураthe mixture was heated at 60°-70° C. for approximately 1.5 hours
2. 2
   ТемператураWhile maintaining the temperature at 60° C.
3. 3
   workup.ADDITIONAfter complete addition
4. 4
   Температураto cool to room temperature
5. 5
   workup.STIRRINGwas stirred for approximately 18 hours
6. 6
   ДругоеThe mixture was partitioned between dilute aqueous hydrochloric acid and ethyl acetate
7. 7
   СушкаThe organic phase was dried over anhydrous magnesium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   ДругоеEvaporation of the filtrate under reduced pressure
10. 10
    Другоеproduced an oil
11. 11
    Промывкаeluting with ethyl acetate:n-heptane (1:1)
12. 12
    ДругоеEvaporation of the appropriate fractions
13. 13
    Другоеprovided a solid which
14. 14
    Другоеwas recrystallized from ethyl acetate

Методика

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.

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