反应详情

To an ice-cold stirring suspension of (3-isopropylisoxazol-5-yl)methanol (0.338 g, 2.4 mmol) in N,N-dimethylformamide (20 mL) was added a solution of N-(chloromethylene)-N-methylmethanaminium chloride (0.36 g, 2.8 mmol) in N,N-dimethylformamide (10 mL). The mixture was stirred at ambient temperature for 30 min and then transferred to a suspended mixture of spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.56 g, 2.0 mmol), cesium carbonate (1.95 g, 6.0 mmol) in N,N-dimethylformamide (4 mL). The reaction mixture was stirred at ambient temperature for 16 h and filtered. The solid was washed with acetone (100 mL). The filtrate was concentrated in vacuo. The residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient) to give 1′-[(3-isopropylisoxazol-5-yl)methyl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one (0.50 g, 60%) as a colorless solid: mp 132-136° C. (diethyl ether/hexanes); 1H NMR (300 MHz, DMSO-d6) 87.34 (ddd, J=7.7, 7.7, 1.2 Hz, 1H), 7.21 (d, J=7.5 Hz, 1H), 7.14 (d, J=7.7 Hz, 1H), 7.08 (ddd, J=7.5, 7.5, 0.8 Hz, 1H), 6.71 (s, 1H), 6.49 (s, 1H), 6.21 (s, 1H), 5.93 (d, J=1.0 Hz, 2H), 5.08 (s, 2H), 4.82 (d, J=9.4 Hz, 1H), 4.72 (d, J=9.4 Hz, 1H), 3.03 (m, 1H), 1.19 (d, J=6.9 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ176.4, 168.9, 166.3, 155.2, 148.3, 141.6, 141.5, 131.4, 128.8, 123.6, 123.2, 119.5, 109.1, 102.8, 101.3, 101.1, 93.2, 79.5, 57.2, 35.6, 25.8, 21.2; MS (ES+) m/z 405.3 (M+1).

1. stirringThe reaction mixture was stirred at ambient temperature for 16 h
2. filtrationfiltered
3. washThe solid was washed with acetone (100 mL)
4. concentrationThe filtrate was concentrated in vacuo
5. customThe residue was purified by column chromatography with ethyl acetate in hexanes (10% to 30% gradient)