N-methoxy-N-methylprop-2-enamide → (E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-N-methoxy-N-methylacrylamide

関与物質

反応手順

2 g (6.02 mmol) of 2-bromo-3-(4-fluorophenyl)-1-isopropyl-1H-indole and 10 ml of DMF are introduced into a 50 ml three-necked round-bottomed flask, which has been purged with nitrogen and is equipped with a magnetic stirrer, thermometer, reflux condenser, gas inlet tube and nitrogen delivery line, and degassing is carried out for 45 min. by introducing nitrogen. 24 mg (1.0 mol %) of the catalyst K4 from WO-A-99/47474 and 0.539 g (6.59 mmol) of sodium acetate are then added and degassing is carried out for a further 15 min. 1.08 g (8.43 mmol) of N-methoxy-N-methylacrylamide (prepared analogously to a procedure of S. Nahm, Tetrahedron Letters 22, 3815 (1981)) are subsequently added and the suspension is heated at reflux for 1.75 hours. A further 0.5 g (4.34 mmol) of N-methoxy-N-methylacrylamide is added and refluxing is carried out for 1.5 hours. Cooling is then carried out followed by dilution with 50 ml of water and extraction three times with 50 ml of ethyl acetate. The combined organic phases are washed three times with 50 ml of water, dried over magnesium sulfate, filtered and concentrated by evaporation. Purification by means of flash chromatography (hexane/ethyl acetate=2:1) yields a yellow solid that is pure according to NMR. Recrystallisation from 94% ethanol yields slightly yellow crystals having a melting point of from 123 to 124° C.

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