反应详情

温度

80 °C

A mixture of methyl 3-(cyanomethoxy)-5-methoxy-1-methyl-1H-indole-2-carboxylate (0.60 g, 2.2 mmol) and triethylamine (0.40 mL, 0.29 g, 2.9 mmol) in 35 mL of tetrahydrofuran in a pressure reaction vessel is treated with Raney cobalt catalyst (0.40 g). The reactor is pressurized with hydrogen (590 psi) and heated at 80° C. for 10 hours. The cooled reaction mixture is filtered and the filtrate evaporated. The oil residue is dissolved in 50 mL of methanol, and sodium methoxide (0.80 g, 15 mmol) is added to the solution. The mixture is heated at reflux for 3 hours, then cooled and evaporated. The residue is distributed between 75 mL of ethyl acetate and 150 mL of brine. The aqueous layer is extracted several times with fresh ethyl acetate. The combined organic layers are washed with brine, dried (anhydrous sodium sulfate) and evaporated. The crude product residue is purified by flash chromatography (silica gel, 5% methanol in dichloromethane elution) to yield 0.18 g (33%) of product. A sample recrystallized from ethyl acetate-hexane has mp 184°-186° C.

1. customin a pressure reaction vessel
2. customThe cooled reaction mixture
3. filtrationis filtered
4. customthe filtrate evaporated
5. dissolutionThe oil residue is dissolved in 50 mL of methanol
6. temperatureThe mixture is heated
7. temperatureat reflux for 3 hours
8. temperaturecooled
9. customevaporated
10. extractionThe aqueous layer is extracted several times with fresh ethyl acetate
11. washThe combined organic layers are washed with brine
12. dry with materialdried (anhydrous sodium sulfate)
13. customevaporated
14. customThe crude product residue is purified by flash chromatography (silica gel, 5% methanol in dichloromethane elution)