反应详情

To a solution of crude 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-6-(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-one, 2-(Boc-amino)ethyl bromide (2.8 g, 12 mmol) and tetrabutylammonium iodide (235 mg, 0.63 mmol) in CH2Cl2/toluene (2 mL/4 mL) was added 40% NaOH aq. solution (20 mL). The mixture was allowed to stir at rt for 20 h. The reaction mixture was diluted with CH2Cl2 (40 mL) and washed with H2O (50 mL). The organic layer was separated, and the aqueous layer was extracted with CH2Cl2 (4×50 mL). The combined organic solution was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography over silica gel eluting with CH2Cl2/methanol (95/5) to provide tert-butyl(2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-isobutyryl-6-(methylsulfonyl)-1H-indol-1-yl)ethyl)carbamate (300 mg, 35% yield for two steps). For 1-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-6-(methylsulfonyl)-1H-indol-2-yl)-2-methylpropan-1-one: LC-MS m/z 556 [M+Na]+. For tert-butyl(2-(5-(((tert-butyldiphenylsilyl)oxy)methyl)-2-isobutyryl-6-(methylsulfonyl)-1H-indol-1-yl)ethyl)carbamate: LC-MS m/z 699 [M+Na]+. 1H NMR (400 MHz, CDCl3): δ 8.20 (s, 1H), 7.93 (s, 1H), 7.72 (dd, J1=8.0 Hz, J2=1.6 Hz, 4H), 7.47-7.35 (m, 7H), 5.21 (s, 2H), 4.72 (d, J=6.8 Hz, 2H), 3.55 (d, J=6.8 Hz, 2H), 3.33-3.26 (m, 1H), 3.00 (s, 3H), 1.46 (s, 9H), 1.30 (d, J=6.4 Hz, 3H), 1.28 (d, J=6.4 Hz, 3H), 1.11 (s, 9H).

1. washwashed with H2O (50 mL)
2. customThe organic layer was separated
3. extractionthe aqueous layer was extracted with CH2Cl2 (4×50 mL)
4. washThe combined organic solution was washed with brine
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by flash chromatography over silica gel eluting with CH2Cl2/methanol (95/5)