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Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 0.166667 h; Stage #2: at 0 - 20℃; for 1 h;
[00169] A solution of 2-iodo-lH-indole (1) (1.50 g, 6.17 mmol) in THF (20 mL) was added to a suspension of 60percent NaH (0.37 g, 9.25 mmol) at 0 °C and the resulting solution was stirred for 10 min. Methyl iodide (1.75 g, 12.3 mmol) was added dropwise and the reaction mixture was allowed to warm slowly from 0 °C to rt over 1 h. The reaction was quenched with saturated NH4CI solution (15 mL) and extracted with ethyl acetate. The organic layer was dried over Na2S04and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to afford 1.27 g (80percent) of the title compound as a pale yellow oil. FontWeight="Bold" FontSize="10" H NMR (400 MHz, CDCI3) δ 7.71 (d, J = 7.6 Hz, 1H), 7.29 (d, J= 8 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 7.06 (t, J= 7.6 Hz, 1H), 6.78 (s, 1H), 3.74 (s, 3H).
Reference：
[1] Tetrahedron Letters, 1997, vol. 38, # 44, p. 7661 - 7664
[2] Tetrahedron Letters, 2005, vol. 46, # 8, p. 1325 - 1328
[3] Organic Preparations and Procedures International, 2001, vol. 33, # 6, p. 615 - 619
[4] Patent: WO2015/197861, 2015, A1, . Location in patent: Paragraph 00168-00169
[5] Journal of Organic Chemistry, 1992, vol. 57, # 8, p. 2495 - 2497
[6] Tetrahedron Letters, 1997, vol. 38, # 39, p. 6787 - 6790
2
[ 603-76-9 ]
[ 75833-63-5 ]
Yield
Reaction Conditions
Operation in experiment
20%
Stage #1: With n-butyllithium In diethyl ether; hexane at 0℃; for 3.5 h; Reflux Stage #2: With iodine In diethyl ether; hexane at 15℃; for 1 h;
To a solution of N-methylindole (7.00 g, 53.40 mmol) in Et2O (160 mL) at 0 °C was added nBuLi (30mL, 2.67 M in hexane, 80.10 mmol). The solution was stirred for 0.5 h at 0 °C and heated at reflux for 3h. After cooling to 15 °C, iodine (14.90 g, 58.70 mmol) was added and stirred for 1h at 15 °C. Thereaction was quenched with 20percent aq. Na2S2O3 (50 mL) and AcOEt (50 mL) was added, the layers wereseparated, and the aqueous layer was extracted with AcOEt (50 mL). The organic layers were combined,washed successively with sat. aq. NaHCO3 (50 mL), H2O (50 mL), dried over MgSO4, and concentratedin vacuo. The residue was purified by recrystallization from petroleum ether (20 mL) to afford 2a (5.78g,42percent yield) as a light brown crystal. The filtrate was concentrated in vacuo, the residue was purified byflash chromatography (silica gel, hexane/AcOEt = 70:1), and then by recrystallization from hexane (15mL) to afford 2a (2.74g, 20percent yield) as a white crystal.
Reference：
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1982, vol. 31, # 11, p. 2226 - 2229[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1982, # 11, p. 2524 - 2527
[3] Angewandte Chemie - International Edition, 2006, vol. 45, # 14, p. 2274 - 2277
[4] Chemistry - A European Journal, 2018, vol. 24, # 15, p. 3725 - 3728
[5] Tetrahedron, 2013, vol. 69, # 45, p. 9481 - 9493
[6] Tetrahedron, 1980, vol. 36, # 10, p. 1439 - 1443
[7] Chemistry - A European Journal, 2010, vol. 16, # 5, p. 1670 - 1678
To a solution of N-methylindole (7.00 g, 53.40 mmol) in Et2O (160 mL) at 0 °C was added nBuLi (30mL, 2.67 M in hexane, 80.10 mmol). The solution was stirred for 0.5 h at 0 °C and heated at reflux for 3h. After cooling to 15 °C, iodine (14.90 g, 58.70 mmol) was added and stirred for 1h at 15 °C. Thereaction was quenched with 20percent aq. Na2S2O3 (50 mL) and AcOEt (50 mL) was added, the layers wereseparated, and the aqueous layer was extracted with AcOEt (50 mL). The organic layers were combined,washed successively with sat. aq. NaHCO3 (50 mL), H2O (50 mL), dried over MgSO4, and concentratedin vacuo. The residue was purified by recrystallization from petroleum ether (20 mL) to afford 2a (5.78g,42percent yield) as a light brown crystal. The filtrate was concentrated in vacuo, the residue was purified byflash chromatography (silica gel, hexane/AcOEt = 70:1), and then by recrystallization from hexane (15mL) to afford 2a (2.74g, 20percent yield) as a white crystal.
To a solution of 2a (1.29 g, 5.02 mmol) in THF (18 mL) at 78 °C was added nBuLi (4.7 mL, 1.58 Min hexane, 7.43 mmol). The solution was stirred at 78 °C for 0.5 h and a solution of 1,2-dibromo-1,1,2,2-tetrachloroethane (2.61 g, 8.02 mmol) in THF (6 mL) was added dropwise. The reaction mixturewas stirred at78 °C for 10 min and 0 °C for 0.5 h, and allowed to stir at RT for 0.5h. The reaction wasquenched with 20percent aq. Na2S2O3 (20 mL) and extracted with AcOEt (3 x 20 mL). The organic layerswere combined, washed with brine (20 mL), dried over MgSO4, and concentrated in vacuo. The residuewas purified by flash chromatography (silica gel, hexane/AcOEt = 10:1) to afford 3a (908 mg, 86percentyield) as a white crystal.
3-(2-iodo-1-methyl-1H-indol-3-yl)propanal[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
59%
[00170] To a stirred solution of acrolein (3) (1.38 g, 24.7 mmol) and N-methylaniline (0.16 g, 1.48 mmol) at 0 °C was added TFA (0.16 g, 1.48 mmol) dropwise and the reaction mixture was stirred at 0 °C for 10 min. 2-Iodo-l -methyl- lH-indole (2) (1.27 g, 4.94 mmol) in CH2C12(4 mL) was added and the reaction mixture was slowly stirred from 0 °C to rt for 3 h. The reaction mixture was diluted with water and extracted with dichloromethane (DCM). The organic layer was dried over Na2S04and concentrated under reduced pressure. The crude material was purified by silica gel chromatography to afford 920 mg (59percent) of the title compound as light yellow foam. NMR (400 MHz, CDCI3) delta 9.85 (s,2H), 7.51 (d, J= 8.0 Hz, 1H), 7.30 (d, J = 8.4Hz, 1H), 7.16(t, J= 9.8 Hz, 1H), 7.08 (t, J= 8 Hz, 1H), 3.75 (s, 3H), 3.75 (s, 3H), 3.09 (t, J = 7.6 Hz, 2H), 2.76 (t, J= 8.2 Hz, 2H); MS (ESI+) m/z = 314 (M+H).
7%
With N-methylaniline; trifluoroacetic acid; In dichloromethane; isopropyl alcohol; at 0 - 20℃; for 15h;
To a solution of acrolein (ca. 90wtpercent, 4.36 g, 70.00 mmol) in CH2Cl2/iPrOH (85:15, 60 mL) at RT wasadded N-methylaniline (175 mg, 1.63 mmol) and trifluoroacetic acid (186 mg, 1.63 mmol). The solutionwas cooled to 0 °C and 2a (6.00 g, 23.34 mmol) was added. The mixture was stirred at 0 °C for 3 h andRT for 12 h, and concentrated in vacuo. The residue was purified by flash chromatography (silica gel,hexane/AcOEt = 20:1), and then by recrystallization from hexane/AcOEt (30:1, 30 mL) to afford 4a(5.36 g, 73percent yield) as a white crystal. The filtrate was concentrated in vacuo, the residue was purified byrecrystallization from hexane/AcOEt (30:1, 10 mL) to afford 4a (0.49 g, 7percent yield) as a slightly greencrystal.
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