Hydrochloric Acid → 9-Benzyl-9-azabicyclo[3.3.1]nonan-3-one

Participants

Reaction Conditions

Reaction Steps

Glutaraldehyde (25% solution in water) (910 mL, 2.4 mol) and benzylamine hydrochloride (344.1 g, 2.4 mol) in water (1050 mL) was cooled to 0° C. 3-Oxopentanedioic acid (350.0 g, 2.4 mol) was added followed by addition of sodium acetate (aq.) (79.7 g in 797 mL water) resulting in formation of a thick orange precipitate. The reaction mixture was heated to 50° C. and stirred at this temperature for 4 h. It was then cooled to ambient temperature and allowed to stand for 24 h. The reaction mixture was acidified to pH2 with 5N aqueous hydrochloric acid (˜150 mL) and the resulting aqueous mixture was washed with diethyl ether (2×500 mL). The aqueous extracts were basified to pH12 with 4N aqueous sodium hydroxide (˜650 mL) and extracted with dichloromethane (6×500 mL). The organic phase was dried (MgSO4) and concentrated under reduced pressure to afford the crude product as a red oil. Purification by chromatography on silica gel with dichloromethane:methanol (49:1, v/v) as eluent afforded 9-benzyl-9-azabicyclo[3.3.1]nonan-3-one (300.0 g, 1.3 mol, 54%) as a pale orange solid.

Provenance & Evidence