N-methyl-2-pyrrolidone → (9R)-4-Chloro-9-(trifluoromethyl)-9H-fluorene-2,9-diol

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Reaction Conditions

Reaction Steps

To 4-[(9R)-4-chloro-9-hydroxy-9-(trifluoromethyl)-9H-fluoren-2-yloxy]butyric acid (50 g) were added N-methylpyrrolidone (200 ml) and pyridine hydrochloride (298 g), and the mixture was stirred at an oil bath temperature of 200° C. for 2 days. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (500 ml), and washed twice with water. The obtained aqueous layer was extracted again with ethyl acetate (300 ml). The combined organic layer was washed successively with water, 1N hydrochloric acid and saturated brine. To the obtained organic layer were added anhydrous magnesium sulfate and activated carbon (10 g), and the mixture was stirred at room temperature. The insoluble material was filtered off through celite. The solvent in the obtained organic layer was evaporated, hexane was added to the residue, and the mixture was stirred at room temperature. The precipitated solid was collected by filtration, and dried under reduced pressure at room temperature. The obtained crude product was dissolved in ethyl acetate (500 ml), washed 3 times with water, dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the solvent in the filtrate was evaporated. To the residue was added hexane, and the mixture was stirred at room temperature. The precipitated solid was collected by filtration, dried under reduced pressure at room temperature to give the title compound (22.4 g).

Provenance & Evidence