Pyridine → (1S,2R)-3-(cyclopropylamino)-1-(3-fluorophenyl)-1-(1H-indol-1-yl)propan-2-ol

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Reaction Steps

(2S,3S)-3-(3-Fluorophenyl)-3-(1H-indol-1-yl)propane-1,2-diol (example 47, step 5) (0.6 g, 2.1 mmol) was dissolved in pyridine (5 mL) and para-toluenesulfonyl chloride (0.44 g, 2.3 mmol) was added. The mixture was stirred for 3 hours then the reaction mixture was diluted with ethyl acetate and washed with water, followed by a saturated aqueous solution of copper sulfate, a 2N aqueous solution of hydrochloric acid, and saturated brine. The organic layer was separated, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The crude product was immediately dissolved in methylamine (8M solution in ethanol, 25 mL) and stirred for 16 hours. The mixture was concentrated in vacuo and purified via flash column chromatography (silica, 5% methanol saturated with ammonia in chloroform) to give (1S,2R)-3-(cyclopropylamino)-1-(3-fluorophenyl)-1-(1H-indol-1-yl)propan-2-ol as a colorless oil. The freebase was dissolved in diethyl ether (5 mL) and treated with a 1N ethereal solution of hydrochloric acid (1 equivalent). The white precipitate was collected and dried under vacuum to give 80 mg (12%) of (1S,2R)-3-(cyclopropylamino)-1-(3-fluorophenyl)-1-(1H-indol-1-yl)propan-2-ol hydrochloride. HRMS: calcd for C20H21FN2O+H+, 325.17107; found (ESI, [M+H]+), 325.1728.

Provenance & Evidence