Citric Acid → (S)-8-Fluoro-6-methyl-5,6-dihydrophenanthridine

Participants

Reaction Conditions

Reaction Steps

To a stirred suspension of lithium borohydride (8.25 g, 0.378 mole) in a mixture of toluene (94.7 niL) and tetrahydrofuran (9.46 mL) kept under nitrogen and at 0° C. was added dropwise chlorotrimethylsilane (96.1 nmL). Additional tetrahydrofuran (30 mL) and toluene (105 mL) were added to rinse the glassware. (R)-2-methyl-CBS-oxazaborolidine (56.8 mL) was added dropwise at room temperature. The mixture was cooled to 0° C. and solid 8-fluoro-6-methylphenanthridine (40 g, 0.189 mole) was added in two portions over a 10 minute and 5 minute period, respectively. The cooling bath was removed, the flask walls rinsed with toluene (60 mL) and the brown slurry was stirred at room temperature. Aliquots were taken at regular intervals to monitor the progress of the reaction. After 8 days the conversion reached 97% . The reaction mixture was cooled to 0° C., treated dropwise with 10% aqueous citric acid (100 mL) under vigorous stirring to control foaming. Ethyl acetate was added (800 mL) followed by more 10% aqueous citric acid (300 mL) and then methanol (300 mL) to redissolve the precipitate. The layers were separated and the organic layer was washed with saturated aqueous sodium bicarbonate (100 mL) and brine (100 mL), dried over anhydrous sodium sulfate and evaporated to dryness to provide 38.4 g (95% yield) of the title compound.

Provenance & Evidence