Pyrrolidine → Indole

Participants

Reaction Steps

A mixture of N-BOC-indole (2.0 g, 6.7 mmol) and 2-formyl benzene boronic acid (1 g, 6.7 mmol) was diluted with THF (20 mL) and 2M sodium carbonate (10 mL), then deoxygenated by a rapid stream of nitrogen applied to the system for 20 min, followed by treatment with Pd(0). The reaction was refluxed for 18 h, cooled down, filtered through Celite® and washed with THF (20 mL). The filtrate evaporated to dryness, taken up in water, and extracted with EtOAc (3×). The EtOAc extracts were dried over sodium sulfate and concentrated. The crude residue (1 g, 1.5 mmol) was treated with sodium borohydride (0.14 g, 1.5 mmol) and pyrrolidine (0.3 mL, 1.5 mmol). The reaction mixture was stirred for 18 h, diluted with ice water and extracted with EtOAc. Ethyl acetate extracts were dried over sodium sulfate and concentrated. The crude residue was purified by flash chromatography (hexane/EtOAc, 1:3) to afford an intermediate indole (0.27 g), that was treated with TFA (10 mL) and sodium cyanoborohydride (43 mg, 0.7 mmol). The reaction mixture was stirred for 4 h, concentrated and purified through a plug of silica gel(hexane/EtOAc, 1:1) to afford the desired product (0.25 g, 29% over last 2 steps). LRMS (ES+): 279.2 (M+H)+.

Provenance & Evidence