Pyridine → methyl 5-bromo-6-chloro-1H-indole-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-6-chloro-1H-indole (15.1 g, 65.5 mmol), tetrahydrofuran (100 mL), pyridine (18.4 mL, 229 mmol) and DMAP (808 mg, 6.55 mmol) was cooled to 0° C. and treated with trichloroacetyl chloride (22.1 mL, 197 mmol) dropwise over 30 minutes. The reaction mixture was stirred at room temperature for 64 hours then cooled to 10° C. Methanol (100 mL) was added dropwise to the reaction mixture over 10 minutes, producing a dark homogenous solution. Potassium carbonate (54.9 g, 393 mmol) was then added portion-wise and the ice bath was removed. Stirring was kept at a vigorous pace and allowed to continue for 2 hours, during which time the reaction turned dark green and produced an exotherm. The reaction was quenched slowly with 1 M HCl (until acidic pH was maintained) and diluted with ethyl acetate. The organic layer was washed with 1 M HCl. The aqueous layer was back-extracted twice with ethyl acetate. The combined organic layers were then washed carefully with saturated sodium bicarbonate solution followed by brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to provide the title compound as a brown solid (18.7 g, 99%).

Provenance & Evidence