Triethylamine → Naltrexone

Participants

Reaction Conditions

Reaction Steps

Cyclopropylmethyl bromide (64 mg; 0.479 mmol) and Et3N (45 μl; 0.327 mmol) were added to a suspension of noroxymorphone (Example 5, 100 mg; 0.348 mmol) in a mixture of N-Methyl-2-pyrrolidone (NMP)/H2O (10:1; 0.35 mL). The reaction vessel was purged with argon and the reaction mixture was stirred at 70° C. for 2 h. At that time, additional Et3N (45 μl; 0.327 mmol) was added and the mixture was stirred for an additional 6 h at 70° C. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (15 mL) and washed with saturated NaHCO3 (3×3 mL). The aqueous layer was re-extracted with dichloromethane (5 mL) and the combined organic layers were dried over MgSO4. Column chromatography of the residue (dichloromethane/methanol 4:1) afforded 103 mg (87%) of naltrexone as a white solid: mp 173-175° C. (acetone), mp 159-161° C. (MeOH), [lit. mp 174-176° C. (acetone)]xvii identical in all respects to the material described in the literature.xviii

Provenance & Evidence