反応 #1267670

反応方程式

iodoethane

4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid

potassium carbonate

cesium carbonate

→

ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid

収率 86.9%

溶媒

N,N-dimethylformamide

反応条件

後処理

1. 1
   温度After cooling to ambient temperature
2. 2
   ろ過the mixture is filtered
3. 3
   洗浄the solid is rinsed with ethyl acetate
4. 4
   濃縮the filtrate concentrated in vacuo
5. 5
   workup.ADDITIONWater (2 L) is added
6. 6
   抽出then extracted with ethyl acetate (2×2 L)
7. 7
   洗浄the combined organic extracts are washed with brine
8. 8
   乾燥dried over magnesium sulfate
9. 9
   ろ過filtered
10. 10
    濃縮concentrated in vacuo

実験手順

To a stirred mixture of 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (640 g, 3.55 mol), potassium carbonate (1.7 kg, 10.65 mol) and cesium carbonate (100 g, 0.32 mol) in N,N-dimethylformamide (9.0 L) is added iodoethane (1250 g, 8.01 mol). The mixture is heated at 60° C. for 2 h. After cooling to ambient temperature, the mixture is filtered, the solid is rinsed with ethyl acetate, and the filtrate concentrated in vacuo. Water (2 L) is added then extracted with ethyl acetate (2×2 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (642 g). A mixture of this ester (640 g, 3.07 mol) and ammonium acetate (426 g, 5.53 mol) in N,N-dimethylformamide (320 mL) is heated to 100° C. for 2 h. The reaction mixture is concentrated in vacuo, ice water (2.5 L) is added, and extracted with dichloromethane (2×3 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (357 g). A mixture of this ester (170 g, 0.82 mol) in ethyl alcohol (250 mL) and a solution of sodium hydroxide (165 g, 4.1 mol) in water (1 L) is heated at reflux for 1 h, then cooled in an ice water bath. Concentrated hydrochloric acid (350 mL) is added dropwise, the precipitate collected by filtration, rinsed with ice water (3×), and dried in a vacuum oven at 75° C. to afford 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (125 g). m.p. 269-270° C.

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