反应详情

A 50% solution of sodium hydroxide (100 ml) was added to a vigorously stirred solution of indole (5.8 g, 50 mmol) and tetrabutylammonium hydroxide (40% by weight solution, 2 ml, 3.1 mmol) in tetrahydrofuran (100 ml). After 5 minutes, a solution of 2-acetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride (R. G. Pendleton et al., J. Pharmacol. Exp. Ther., 1979, 208, 24; U.S. Pat. No. 3,725,388 (1973)) (13.7 g, 50 mmol) in tetrahydrofuran (50 ml) was added over 10 minutes and the resulting mixture was vigorously stirred for a further 3 h. The mixture was then extracted with ethyl acetate (250 ml) and the extract dried (MgSO4), concentrated in vacuo and the residue purified by column chromatography over silica gel eluting with a dichloromethane/methanol gradient to give the title compound (D1) (12.8 g, 72%), NMR (CDCl3; rotamers observed)/ppm 2.12, 2.14 (3H, 2×s), 2.77-2.88 (2H, m), 3.60, 3.74 (3H, 2×t J=7 Hz), 4.59, 4.68 (2H, 2×s), 6.65-6.67 (1H, m), 7.16-7.34 (3H, m), 7.50-7.69 (4H, m), 7.94-7.99 (1H, m); MS: m/z (MH+) 355.

1. extractionThe mixture was then extracted with ethyl acetate (250 ml)
2. dry with materialthe extract dried (MgSO4)
3. concentrationconcentrated in vacuo
4. customthe residue purified by column chromatography over silica gel eluting with a dichloromethane/methanol gradient