Ethyl Acetate → 6beta-Naltrexol

Participants

Reaction Steps

To a suspension of naltrexone base 3 (6.81 g, 20.0 mmol) (Mallinckrodt, St. Louis, Mo.), under argon was added 100 ml (enough to afford complete solution) of 0.533M aqueous NaOH. The alkaline solution of naltrexone was treated dropwise at ambient temperature during 20 min. with 8.64 g (80 mmol) of formamidinesulfinic acid dissolved in 200 ml of 0.533M aqueous NaOH. After the addition was complete, the solution was heated and stirred at 80°-85° C. for 1.5 h when TLC indicated the reaction to be complete. The reaction mixture was cooled (ice-bath) and then treated dropwise under argon with a solution of ammonium chloride (10.27 g, 192 mmol) in distilled water (100 ml). The aqueous mixture was extracted with 5×100 ml of CHCl3 and the combined organic extract was filtered through a pad of Na2SO4 and evaporated in vacuo to afford crude 5.(base) as a foam which was dissolved in 20 ml of warm (50° C.) ethyl acetate and diluted to 60 ml with warm n-hexanes. Crystallization occurred spontaneously on cooling. The crystals were collected by filtration, washed with 2×10 ml of cold ethyl acetate/n-hexanes (1:3), and oven dried in vacuo at 60° C. to give 5 (6.11 g, 89%) (free of any 6α-epimer 4): [α]D =-156° (c 0.604, MeOH). mp 707°-708° C.

Provenance & Evidence