Cyclopropanecarboxaldehyde → Naltrexone

Participants

Reaction Steps

A round bottom flask was charged with noroxymorphone (2.19 g, 0.008 moles), isopropanol (20 mL), and cyclopropanecarboxaldehyde (1.07 g, 0.02 moles, 0.91 mL). Ammonium formate (2.40 g, 0.038 moles) was added. To this solution was added RuCl3 (anhydrous)(10 mg, 0.05 mmole). The reaction mixture was stirred at room temperature for 24 h. HPLC analysis indicated the reaction was complete. To the reaction mixture was added distilled water (1.0 mL) and the mixture was stirred for 16 h at room temperature. Then, the reaction mixture was transferred to a round bottom flask and evaporated under reduced pressure leaving a semi solid. To the semi solid was added distilled water (10 mL). To this solution was added 29% NH3/H2O (˜5 mL) adjusting the pH from 7.0 to 9.4. A white precipitate formed. The precipitate was filtered, washed with distilled water (10 mL), and dried for 16 h at 95° C. yielding (−)-naltrexone (2.35 g, 0.007 moles, 91% yield) as an off white solid.

Provenance & Evidence