4-Aminophenol → 4-(Pyridin-4-yloxy)aniline

Participants

Reaction Steps

A solution of 4-aminophenol (15 g, 0.135 mol), 4-chloropyridine hydrochloride (22.5 g, 0.148 mol), and KOtBu (45.8 g, 0.404 mol) in DMPU (208 ml) and DMF (52 ml) is stirred at 100° C. for 24 h, cooled to rt, poured into H2O (0.6 L), and extracted with AcOEt (150 ml, 6×). The combined organic phases are washed with H2O (100 ml, 2×), brine (100 ml, 2×), dried (Na2SO4), concentrated under reduced pressure, and flash chromatographed (silica gel, 4.5×25 cm; AcOEt/hexane=1:9→3:7) to give the title compound of Stage 1.1 as a colorless solid: M+H=187.2; 1H-NMR (400 MHz, DMSO-d6): 8.37 (d, 6.5 Hz, 2H, pyridinyl), 6.79 (d, 9.5 Hz, 2H, phenyl), 6.78 (d, 9.5 Hz, 2H, pyridinyl) 5.12 (s, 2H, NH2); Rf (AcOEt/CH2Cl2=3:7): 0.23; m.p.=165.8-166.6° C.

Provenance & Evidence