5-isopropoxy-2-methyl-1H-indole synthesis

Yield:1134334-84-1 69%

Reaction Conditions:

with triphenylphosphine;diethylazodicarboxylate in dichloromethane at 20;

Steps:

4.1.28. 5-Isopropoxy-2-methyl-1H-indole (44)

At RT, diethyl azodicarboxylate (DEAD, 0.672 mL, 4.27 mmol) was slowly added to a solution of 2-methyl-1H-indol-5-ol (43, 0.42 g, 2.85 mmol), Ph₃P (1.49 g, 5.7 mmol) and propan-2-ol (0.214 g, 3.56 mmol), in 40 mL of CH₂Cl₂. The mixture was stirred at RT until the reaction was complete (TLC analysis) and then quenched with methanol (3 mL).Water was added and the mixture was extracted with CH₂Cl₂. The organic extracts were washed with water and brine, dried over MgSO₄, and concentrated to give the crude product. Purification was performed using flash chromatography on silica gel (isooctane/ethyl acetate, gradient) to give the title compound in 69% yield (0.31 g, 1.63 mmol). MS m/z (relative intensity, 70 eV) 189 (M⁺, 40), 147 (bp), 146 (72), 118 (13), 117 (11).ESIMS: m/z 190.0 (M + H)⁺. ¹H NMR (CD₃OD, 300 MHz) δ: 1.26 (d, J = 6 Hz, 6H), 2.36 (s, 3H), 4.42 (pentamer, J = 6 Hz, 1H), 6.01 (s, 1H), 6.64 (dd, J = 8.7, 2.4 Hz, 1H), 6.94 (d, J = 2.4 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H). ¹³C NMR (CD₃OD, 75 MHz) δ: 13.52, 22.59, 72.95, 100.18, 107.30, 111.66, 113.36, 131.01, 133.63, 137.42, 152.46.

References:

Mattsson, Cecilia;Svensson, Peder;Boettcher, Henning;Sonesson, Clas [European Journal of Medicinal Chemistry,2013,vol. 63,p. 578 - 588]