Ammonium Hydroxide → HCID 12051397, compound

Participants

Reaction Conditions

Reaction Steps

2-(5-Bromo-3-pyridyl)-1-azabicyclo[2.2.2]octane (120 mg, 0.449 mmol) was mixed with aqueous ammonium hydroxide (20 mL, 28%) in a sealed tube, then copper sulfate (200 mg) was added and the reaction mixture was heated at 180° C. for 14 h. The reaction mixture was allowed to cool to ambient temperature and then extracted with chloroform (4×20 mL). The combined organic extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to afford a dark syrup. This crude product was subjected to column chromatography, using chloroform methanol: triethylamine (9:1:1) as eluent, to yield 2-(5-amino-3-pyridyl)-1-azabicyclo[2.2.2]octane as a light brown solid (20 mg). An impure fraction was also obtained, which afforded a brown solid (40 mg), found to be mostly the desired compound with minor impurities (total yield ˜65%). A sample of the free base (20 mg, 0.098 mmol) was dissolved in ethanolic HCl (2 mL) and the mixture sonicated for 5 min. The solvent was removed by rotary evaporation to yield a viscous oil, which solidified upon standing. Recrystallization from ethanol: ether (9:1) afforded the trihydrochloride salt of the product as a brown solid (20 mg), m.p. 210° C. with decomposition.

Provenance & Evidence