Hydrochloric Acid → 1H-Indole-1-acetic acid

Participants

Reaction Conditions

Reaction Steps

1H-indole (5.0 g, 42.7 mmol) in anhydrous DMF (10 mL) was added to a suspension of sodium hydride (1.13 g, 46.9 mmol) in anhydrous DMF (20 mL) in a flame dried flask at 0° C. stirred under nitrogen atmosphere. Fifteen minutes after gas evolution had ceased, bromo-acetic acid ethyl ester (5.7 mL, 51.2 mmol) was added and the reaction was heated to 70° C. and stirred under nitrogen. Upon completion (TLC: 50% dichloromethane in heptane), the reaction mixture was quenched with water (50 mL) and extracted with diethyl ether (3×50 mL). The combined extract was washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. To a solution of crude indol-1-yl-acetic acid ethyl ester (9.37 g, 46.2 mmol) in methanol (20 mL) and THF (80 mL) was added 6N NaOH solution (25 mL). Upon completion (TLC: 10% methanol in dichloromethane), the mixture was acidified with 6N HCl solution to pH 2, and extracted with ethyl acetate (3×75 mL). The combined extract was washed sequentially with water and brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to yield the crude titled compound as a light brown solid. 1H NMR (DMSO-d6, 300 MHz) δ 7.51 (1H, dd, J=8, 1 Hz, Ar—H), 7.35 (1H, dd, J=8, 1 Hz, Ar—H), 7.30 (1H, d, J=3 Hz, Ar—H), 7.09 (1H, td, J=7.5, 1 Hz, Ar—H), 6.99 (1H, td, J=7.5, 1 Hz, Ar—H), 6.41 (1H, dd, J=3, 1 Hz, Ar—H), 4.99 (2H, s, CH2).

Provenance & Evidence