Sodium Chloride → Tert-butyl 5-pyridin-4-yl-indole-1-carboxylate

Participants

Reaction Steps

A mixture of pyridine-4-boronic acid (5.0 g, 0.041 mol), tert-butyl 5-bromo-indole-1-carboxylate (11.8 g, 0.04 mol), 2 M aqueous sodium carbonate (80 mL, 0.16 mol), tetrakis(triphenylphosphine)palladium(0) (0.92 g, 0.0008 mol), ethanol (19 mL) and toluene (175 mL) was boiled under reflux for 12 h. The experiment was repeated with the double amount of starting materials, e.g. 10 g of pyridine-4-boronic acid. The combined reaction mixture from the two experiments was poured onto a saturated sodium chloride solution (brine), and the aqueous phase was extracted with ethyl acetate. The combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (ethyl acetate followed by ethyl acetate/triethylamine 95:5) to give tert-butyl 5-pyridin-4-yl-indole-1-carboxylate (25.5 g, 61%), which was dissolved in a mixture of methanol (500 mL), tetrahydrofuran (200 mL) and 15% aqueous sodium hydroxide (25 mL). The mixture was boiled under reflux for 1 h, concentrate in vacuo to 200 mL and poured onto brine. The aqueous phase was extracted with a mixture of ethyl acetate and tetrahydrofuran, and the combined organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The residue was precipitated from a cold mixture of methanol and tetrahydrofuran to give the title compound as a creamy solid (9.5 g, 54%). A second crop of the title compound was obtained from the mother liquor (1.7 g, 9%).

Provenance & Evidence