Water → HCID 44595323, compound

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 2-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)ethanamine (500 mg, 1.3 mmol) in DMSO (1 mL) was added 2-chloro-4-trifluoromethylpyridine (256 mg, 2.0 mmol, 1.5 equiv.) and diisopropyl ethyl amine (578 μL, 3.3 mmol, 2.5 equiv.). The resulting solution was stirred at 100° C. for 12 hr, after which time HPLC analysis indicated that the reaction was complete. The mixture was brought to 80° C., water (3 mL) was added, and the resulting suspension was stirred for 30 min. The mixture was subsequently brought to ambient temperature and stirred for an additional 30 min, after which the solids were collected by filtration. After drying in vacuo, 750 mg crude brown solids were obtained containing the desired product. The crude material was taken up in trifluoroacetic acid (6 mL) and treated with thioanisole (393 μL, 3.35 mmol). After stirring at ambient temperature for 1 hour, HPLC analysis indicated that the reaction was complete. Volatiles were removed in vacuo and the residue was taken up in 25 mL ethyl acetate. The organic layer was washed with water, 1 M aqueous sodium bicarbonate, and brine (10 mL each), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude hydroquinone (450 mg) was dissolved in acetonitrile (7 mL) and cooled in an ice-water bath. To the stirring solution was added an aqueous solution of ceric ammonium nitrate (1.46 g, 7.6 mmol in 2 mL) in a dropwise fashion. The reaction was deemed complete by TLC analysis when approximately 90% of the reagent was added. At this point, the mixture was partitioned between ethyl acetate and brine (15 mL each), and the organic layer was removed. The remaining aqueous layer was made basic by addition of 10 mL 1 M aqueous sodium bicarbonate, and extracted with ethyl acetate (15 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to produce 500 mg brown oil. Purification by silica gel chromatography (gradient elution 0→35% ethyl acetate in heptane) afforded 2,3,5-trimethyl-6-(2-(4-(trifluoromethyl)pyridin-2-ylamino)ethyl)cyclohexa-2,5-diene-1,4-dione as a bright yellow solid (85 mg). 1H-NMR (400 MHz, CDCl3) 8.15 (d, 1H), 6.76 (m, 2H), 3.49 (m, 2H), 2.86 (t, 2H), 2.08 (s, 3H), 2.01 (s, 6H). M+=338.0.

Provenance & Evidence