Toluene → 8-Methyl-3-(3-trifluoromethylphenyl)-3,8-diazabicyclo[3.2.1]octane

Participants

Reaction Conditions

Reaction Steps

8-Methyl-3,8-diaza-bicyclo[3.2.1]octane (0.25 g, 1.98 mmol) (see, U.S. Pat. No. 3,951,980), 1-bromo-3-trifluoromethylbenzene (0.22 ml, 1.80 mmol), tris(dibenzylideneacetone)dipalladium(0)(0.016 g, 0.018 mmol), (s)-(−)-2,2′-bis(diphenylphosphino)-1-1″-binaphthyl (0.011 g, 0.014 mmol), sodium tert-butoxide (0.24 g, 2.52 mmol) and toluene (5 ml) were combined in a sealed tube and heated at 80° C. for 15 hours. The reaction was cooled to room temperature, diluted with water (100 ml) and extracted with ethyl acetate (3×100 ml). The combined organic layer was washed with water (1×100 ml), dried with magnesium sulfate and evaporated to a brown oil. Silica gel flash chromatography using 5% methanol/chloroform as the eluent yielded 8-methyl-3-(3-trifluoromethylphenyl)-3,8-diazabicyclo[3.2.1]octane (0.15g, 30.8% yield) as a golden oil. The oil was dissolved in 1N hydrochloric acid/methanol (30 mL) and concentrated to yield the hydrochloride salt as a pale yellow foam. 1H NMR DMSO-d6 δ: 11.30 (s, 1H), 7.41 (t, J=8.3 Hz, 1H), 7.20-7.03 (m, 3H), 4.02 (brd s, 2H), 3.75 (d, J=12.9 Hz, 2H),3.37 (d, J=12.0 Hz, 2H), 2.69 (d, J=5.0 Hz, 3H), 2.22-2.09 (m, 2H), 1.99-1.89 (m, 2H).

Provenance & Evidence