反应详情

To a solution of 2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.753 g, 2.55 mmol), [4-(trifluoromethyl)pyridin-2-yl]methanol (Ashimori et al., Chem. Pharm. Bull. (1990) 38:2446-2458) (0.655 g, 3.70 mmol) and tri-n-butylphosphine (0.93 mL, 3.7 mmol) in anhydrous tetrahydrofuran (20 mL) and anhydrous dimethylsulfoxide (0.2 mL) at ambient temperature was added over a period of 10 min a solution of diethyl azodicarboxylate (0.64 mL, 4.1 mmol) in anhydrous tetrahydrofuran (10 mL). The reaction mixture was stirred at ambient temperature for 3 h and was poured into 1 M hydrochloric acid (50 mL). The mixture was extracted with diethyl ether (3×50 mL) and the combined organic extracts were washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography and eluted with a 80% to 100% gradient of dichloromethane in hexanes, followed by a 0% to 20% gradient of ethyl acetate in dichloromethane and recrystallization from methanol afforded 1′-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.164 g, 10%) as a colorless solid: mp 154-155° C. (methanol); 1H NMR (300 MHz, CDCl3) δ8.76 (d, J=5.1 Hz, 1H), 7.51 (s, 1H), 7.44 (d, J=5.1 Hz, 1H), 7.24-7.16 (m, 2H), 7.08-7.01 (m, 1H), 6.86 (d, J=7.7 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H), 5.27 (d, J=16.1 Hz, 1H), 5.04 (d, J=16.1 Hz, 1H), 4.95 (d, J=9.0 Hz, 1H), 4.69 (d, J=9.0 Hz, 1H), 4.23-4.11 (m, 4H); 13C NMR (75 MHz, CDCl3) δ177.8, 157.3, 155.3, 150.8, 144.8, 141.9, 139.8, 138.5, 132.3, 129.0, 124.1, 123.9, 121.1, 118.7, 117.6, 111.8, 109.3, 99.5, 80.1, 64.7, 64.0, 58.2, 45.8; MS (ES+) m/z 455.0 (M+1).

1. extractionThe mixture was extracted with diethyl ether (3×50 mL)
2. washthe combined organic extracts were washed with brine (50 mL)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification of the residue by column chromatography
7. washeluted with a 80% to 100% gradient of dichloromethane in hexanes
8. customfollowed by a 0% to 20% gradient of ethyl acetate in dichloromethane and recrystallization from methanol