反応 #9974

反応方程式

dimethylformamide

triethylamine

sodium hydroxide

ethyl thioacetate

1-(4-fluorophenyl)-2-(pyridin-4-yl)ethanone

Phosphorus oxychloride

dimethylformamide

→

title compound

収率 55.0%

5-Ethoxycarbonyl-2-(4-fluorophenyl)-3-(pyridin-4-yl)thiophene

収率 55.0%

溶媒

dichloromethane

water

反応条件

後処理

1. 1
   workup.STIRRINGThe resulting mixture was stirred at 50° C. for 2 hours
2. 2
   温度At the end of this time, the reaction mixture was cooled to room temperature
3. 3
   抽出extracted with dichloromethane
4. 4
   洗浄The organic layer was washed with water
5. 5
   乾燥dried over anhydrous magnesium sulfate
6. 6
   その他the solvent was removed by distillation under reduced pressure
7. 7
   workup.DISSOLUTIONThe residue was dissolved in a mixed solution of dichloroethane (100 ml) and pyridine (15 ml)
8. 8
   workup.STIRRINGThe resulting mixture was stirred at room temperature for 1 hour
9. 9
   workup.WAIT80° C. for 3 hours
10. 10
    温度The resulting mixture was cooled to room temperature
11. 11
    その他partitioned between water and dichloromethane
12. 12
    洗浄The organic layer was washed with water
13. 13
    乾燥dried over anhydrous magnesium sulfate
14. 14
    その他the solvent was removed by distillation under reduced pressure
15. 15
    その他The residue was purified by column chromatography through silica gel (eluent, hexane:ethyl acetate=2:3)

実験手順

Phosphorus oxychloride (7.9 ml, 85 mmol) was added to dimethylformamide (17.04 ml, 220 mmol) dropwise under ice cooling. The resulting mixture was stirred at room temperature for 1 hour. The mixture was then added dropwise under ice cooling to a solution of 1-(4-fluorophenyl)-2-(pyridin-4-yl)ethanone (21.5 g (100 mmol), prepared as described in T. F. Gallagher et al., Bioorg. Med. Chem., 5, 49–64 (1997)) dissolved in a mixed solution of dimethylformamide (140 ml) and dichloromethane (280 ml). The resulting mixture was stirred at 50° C. for 2 hours. At the end of this time, the reaction mixture was cooled to room temperature, water was added, adjusted to pH 9 to 10 by adding an aqueous solution of 6 N sodium hydroxide and then extracted with dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure. The residue was dissolved in a mixed solution of dichloroethane (100 ml) and pyridine (15 ml). To the resulting solution was added ethyl thioacetate (11 ml, 100 mmol), and then triethylamine (25 ml, 180 mmol) with stirring under ice cooling. The resulting mixture was stirred at room temperature for 1 hour, then 80° C. for 3 hours. The resulting mixture was cooled to room temperature and partitioned between water and dichloromethane. The organic layer was washed with water, dried over anhydrous magnesium sulfate and the solvent was removed by distillation under reduced pressure. The residue was purified by column chromatography through silica gel (eluent, hexane:ethyl acetate=2:3), to give the title compound (18.11 g) as a brown viscous oil (yield 55%).

出典