Water → Naloxone 3-methyl ether

Participants

Reaction Steps

To a solution of naloxone (50 g, 125 mmol) in 50 mL of DMF was added K2CO3 (51.8 g, 375 mmol). The resulting suspension was stirred at ambient temperature for 30 min whereupon methyl iodide (7.82 mL, 125 mmol) in 7 mL of DMF was added dropwise via an addition funnel. The suspension was maintained overnight at ambient temperature. The reaction mixture was added to 1 L of H2O and a white precipitate formed. The mixture was stirred for 1 h then filtered to give a white solid. The solid was dissolved in CH2Cl2 (700 mL) and washed with 1 N NaOH (400 mL). The layers were separated and the organic layer was concentrated to give a wet solid. Water was added and the solid was subsequently filtered and dried overnight in a vacuum oven to afford 28.1 g (66%) of Compound 2 as a white solid. LC/MS, m/z=342.2 [M+H]+ (Calc: 342.40).

Provenance & Evidence