تفاعل #1145326

معادلة التفاعل

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

المردود 86.9%

المذيبات

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter cooling to ambient temperature
2. 2
   ترشيحthe mixture is filtered
3. 3
   غسيلthe solid is rinsed with ethyl acetate
4. 4
   تركيزthe filtrate concentrated in vacuo
5. 5
   workup.ADDITIONWater (2 L) is added
6. 6
   استخلاصthen extracted with ethyl acetate (2×2 L)
7. 7
   غسيلthe combined organic extracts are washed with brine
8. 8
   تجفيفdried over magnesium sulfate
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated in vacuo

الإجراء التجريبي

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.

المصدر