Phenol → HCID 21913948, compound

Participants

Reaction Conditions

Reaction Steps

Phenol (5.33 g, 56.63 mmol) was added in small portions over a period of 10 minutes to a chilled (0°) suspension of sodium hydride (2.39 g of 60%, 59.75 mmol) in anhydrous tetrahydrofuran (100 mL). After the addition was complete, the reaction was allowed to stir at 0° for 30 minutes. A solution tert-butyl 2-{2-[(2-chloro-5,6-dimethyl-3-nitropyridin-4-yl)amino]ethoxy}ethylcarbamate (20.67 g, 53.16 mmol) in tetrahydrofuran (100 mL) was added over a period of 1 hour while maintaining the temperature at 0° C. The ice bath was removed and the reaction mixture was heated to reflux. At 46 and 52 hours additional fresh sodium phenoxide (11.3 mmol) was added. Refluxing was continued for 2 hours after the second addition. The reaction mixture was diluted with ethyl acetate (500 mL); washed sequentially with water (3×100 mL), 1N sodium hydroxide (2×100 mL), and brine; dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by column chromatography (450 g of silica gel eluting with 1/1 hexanes/ethyl acetate) to provide 19.85 g of tert-butyl 2-{2-[(2,3-dimethyl-5-nitro-6-phenoxypyridin-4-yl)amino]ethoxy}ethylcarbamate.

Provenance & Evidence