反应详情

温度

0 °C

To a stirred solution of the 1-benzyl-2-(6-methoxy-2-naphthyl)-3-pentyl-1H-indole (109.0 g, 251 mmol) in CH2Cl2 (1000 mL) under N2 at −78° C. was added BBr3 (1M in CH2Cl2, 302 mL), dropwise, over 1.5 h. After the addition, the reaction was warmed to 0° C. and stirred for 2.5 h then warmed to rt. After a total of 5 h the reaction mixture was cooled to 0° C. and quenched with water (250 mL). The mixture was stirred overnight then rotovap'd to a residue. The residue was partitioned between EtOAc (1500 mL) and H2O (500 mL). The layers were shaken, separated, and the organic layer was washed with H2O (2×250 mL), brine (2×250 mL), dried over Na2SO4, filtered, rotovap'd and dried in vacuo to give a viscous black goo (114 g). The residue was dissolved in CHCl3 and flashed on silica (2000 g). The column was eluted with hexane and 8% EtOAc/Hexane. The product was collected, filtered, rotovap'd and the residue triturated with hexane then dried to give the product as an off-white solid (89.2 g, 213 mmol, 85%) with mp 96-100° C. 400mg of the crude solid was recrystallized from hexane to give desired product as an off-white solid (311 mg) with mp 97-100° C.; 1H NMR (DMSO-d6) δ 0.73 (t, J=6.7 Hz, 3H), 1.10-1.20 (m, 4H), 1.51-1.60 (m, 2H), 2.67 (t, J=7.3 Hz, 3H), 5.29 (s, 2H), 6.82 (d, J=7.2 Hz, 2H), 7.04-7.20 (m, 7H), 7.30-7.35 (m, 2H), 7.59 (d, J=7.8 Hz, 1H), 7.73-7.78 (m, 3H); IR (solid) 3380, 2920, 1610, 1200, 740 cm−1; mass spectrum [ES], m/z 420 (M+H)+;

1. additionAfter the addition
2. temperaturethen warmed to rt
3. temperatureAfter a total of 5 h the reaction mixture was cooled to 0° C.
4. customquenched with water (250 mL)
5. stirringThe mixture was stirred overnight
6. customThe residue was partitioned between EtOAc (1500 mL) and H2O (500 mL)
7. stirringThe layers were shaken
8. customseparated
9. washthe organic layer was washed with H2O (2×250 mL), brine (2×250 mL)
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. customdried in vacuo
13. customto give a viscous black goo (114 g)
14. washThe column was eluted with hexane and 8% EtOAc/Hexane
15. customThe product was collected
16. filtrationfiltered
17. customrotovap'd and the residue triturated with hexane
18. customthen dried