[2-(7-benzyloxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester → [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

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Reaction Conditions

Reaction Steps

A mixture of [2-(7-benzyloxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (20.75 g, 52.6 mmol), 5% Pd/C (1.00 g, 5 wt %), and 3A ethanol (200 mL) is pressurized to 55 psig with H2, and is heated to 50° C. After 40 minutes, the slurry is filtered, and the filtrate is concentrated to give 15.41 g of [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (96%). FDMS m/e=305 (M++1). To a solution of [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (6.04 g, 19.8 mmol) in dichloromethane (125 mL) is added triethylamine (14 mL, 99.2 mmol). The mixture is cooled to 0° C. and trifluoromethanesulfonyl anhydride (4.4 mL, 25.8 mmol) is added dropwise as a solution in dichloromethane (25 mL). The mixture is warmed to ambient and stirred overnight. The solution is diluted with brine and extracted three times with dichloromethane. The combined organics are dried over anhydrous sodium sulfate then filtered and evaporated. The residue is purified using silica gel chromatography (hexane/20% ethyl acetate in hexane gradient elution) to give 7.199 g of trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (83%). FDMS m/e=437 (M++1).

Provenance & Evidence