Hydrochloric Acid → 5-Chloro-2-(1-methylpropyl)indole

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl (4-chloro-2-methylphenyl)carbamate (338 mg) in tetrahydrofuran (6 mL) was added dropwise sec-butyllithium (1.04 mol/L hexane-cyclohexane solution, 2.69 mL) at −70° C. under an argon atmosphere. The mixture was warmed to −40° C. and then stirred for 10 minutes. Then a solution of N-methoxy-N,2-dimethylbutanamide (203 mg) in tetrahydrofuran (0.5 mL) was added dropwise, and the mixture was stirred at −40° C. for 40 minutes. The mixture was stirred at room temperature for additional 2 hours. 1 mol/L Hydrochloric acid (2.8 mL) was added to the reaction mixture under cooling with ice, and this resulting mixture was extracted with diethyl ether. The organic layer was washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue (446 mg) was dissolved in dichloromethane (4 mL). Trifluoroacetic acid (0.8 mL) was added and this resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was diluted with dichloromethane, washed successively with water and a saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (173 mg).

Provenance & Evidence