Hydrochloric Acid → Methyl indole-3-acetate

Participants

Reaction Steps

A mixture of commercially available (1H-indol-3-yl)acetic acid (200 g, 1.14 mol), methanol (2700 mL) and a saturated solution of HCl in diethyl ether (750 mL) was stirred at room temperature for 16 h. The solvent was removed in vacuo, and the residue was subjected to aqueous work-up under alkaline conditions by the use of aqueous ammonia to yield methyl (1H-indol-3-yl)acetate as an oil (202.5 g, 94%). The crude oil was dissolved in acetic acid (2 L), and sodium cyanoborohydride (60 g, 0.95 mol) was added in portions of 1 g over a period of 8 h. The resulting mixture was stirred at room temperature for 16 h and then poured onto an ice/water mixture. Aqueous work-up under alkaline conditions gave the crude product that was purified by flash chromatography (ethyl acetate/heptane 1:1) to give the title compound (97.3 g, 48%).

Provenance & Evidence