Hexane → 2-((2-(6-Amino-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanol

Participants

Reaction Steps

A suspension of tris(dibenzylideneacetone)dipalladium(0) (48 mg, 0.053 mmol) in anhydrous THF (3 mL) was treated with tri-t-butylphosphine in hexane (10% wt) (0.320 mL, 0.105 mmol) and the mixture stirred for 5 minutes at room temperature. A solution of 2-((2-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)ethyl)(methyl)amino)ethanol (compound 2, 0.165 g, 0.527 mmol) in THF (7 mL) was added followed by lithium bis(trimethylsilyl)amide (1M in THF, 1.58 mL, 1.58 mmol) and the mixture heated in a sealed reaction vial at 90° C. for 3 hours. The mixture was cooled to room temperature then to 0° C. and quenched with 3N aq. HCl (1.5 mL) and stirred for 30 minutes slowly warming to room temperature. The mixture was diluted with ethyl acetate, basified to pH ˜10 by the addition of 1N aq NaOH and transferred to a separatory funnel. The organic layer was separated and the aqueous layer further extracted with ethyl acetate (×3) and the combined organic layers washed with brine, dried over Na2SO4, filtered and concentrated to give a dark brown residue. Purification on silica gel eluting with 7.5% 2M NH3 in methanol/92.5% dichloromethane yielded an orange-red residue, 3 (57 mg, 43.4%). 1H-NMR (DMSO-d6) δ 6.36-6.27 (m, 2H), 6.21 (br s, 1H), 4.31 (t, 1H, J=5.4 Hz, exch. D2O), 4.18 (br s, 2H, exch. D2O), 3.44 (q, 2H, J=6.3 Hz), 3.18 (t, 2H, J=7.3 Hz), 3.10 (t, 2H, J=5.3 Hz), 2.56-2.40 (2×m, 6H), 2.22 (s, 3H), 1.84-1.72 (m, 2H). MS (ESI+): 250 (MH+, 100).

Provenance & Evidence