Nitrogen → 4-[6-(Tert-butyldimethylsilanyloxymethyl)-pyridin-2-yl]morpholine

Participants

Reaction Conditions

Reaction Steps

A solution of 2-bromo-6-(tert-butyldimethylsilanyloxymethyl)pyridine (J. Org. Chem.; 1993; 4389-4397) (500 mg, 1.66 mmol), morpholine (173 μl, 2.0 mmol), 1,3-bis(diphenylphosphino)propane (68 mg, 10 mol %) in toluene (20 ml) was degassed with a stream of N2 for 15 min. Sodium tert-butoxide (222 mg, 2.31 mmol) and Pd2(dba)3 (76 mg, 5 mol %) were added and the reaction mixture was heated at 70° C. overnight under N2. After cooling to room temperature, Et2O (100 ml) was added and the solution was washed with brine (25 ml), dried and concentrated under reduced. The mixture was purified by column chromatography on silica using 30% Et2O/iso-hexanes as eluent to yield the desired aminopyridine (370 mg, 72%). 1H NMR (400 MHz, CDCl3) δ 7.40 (1H, dd, J=8.6, 7.4 Hz), 6.75 (1H, d, J=7.4 Hz), 6.38 (1H, d, J=8.6 Hz), 4.56 (2H, s), 3.70 (4H, t, J=5.0 Hz), 3.36 (4H, t, J=5.0 Hz), 0.84 (9H, s), 0.00 (6H, s). m/z (ES+) 309 (M+H+).

Provenance & Evidence