Formic Acid → Naltrexone Base

Participants

Reaction Steps

Into a round bottom flask was charged noroxymorphone (2.00 g, 0.007 moles), triethylamine (3.52 g, 0.035 mole, 4.85 mL), acetonitrile (15 mL), and cyclopropanecarboxaldehyde (0.98 g, 0.014 mole, 0.92 mL). The mixture was stirred for about 5 minutes at room temperature then >96% formic acid (4.0 g, 0.87 mole, 3.28 mL) was added dropwise. After stirring the mixture for 15 minutes at room temperature, dichloro(p-cymene)Ru(II) dimer (10 mg, 0.000014 moles) was added. The mixture was then stirred at room temperature for about 24 hours. HPLC indicated the reaction was complete. The reaction mixture was evaporated to a thick oil, and distilled water (5.0 mL) was added. The pH was adjusted to 9.4 using 29% NH3/H2O where a precipitate formed. The mixture was stirred overnight at room temperature. The precipitate was filtered, washed with distilled water (10 mL), and dried at 90° C. for about 24 hours. The dried precipitate yielded naltrexone base (2.28 g, 95% yield).

Provenance & Evidence