4-Aminophenol → 4-(4-Aminophenoxy)-N-methylpicolinamide

Participants

Reaction Steps

A solution of 4-aminophenol (9.6 g, 88 mmol) in anhydrous DMF (100 mL) was treated with NaH (5.28 g of a 60% dispersion, 132 mmol), and the reddish-brown mixture was stirred at RT for 2 h. The contents were treated with 4-chloro-N-methylpicolinamide (15 g, 88 mmol) and K2CO3 (6.5 g, 44 mmol) and heated at 80° C. for 8 h. The mixture was cooled to RT and partitioned between EtOAc and brine. The aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine (2×50 mL), dried (Na2SO4) and concentrated to afford 4-(4-amino-phenoxy)pyridine-2-carboxylic acid methylamide (15 g, 71% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.71 (d, J=1.8 Hz, 1H), 8.43 (d, J=5.7 Hz, 1H), 7.32 (d, J=2.7 Hz, 1H), 7.06-7.03 (m, 1H), 6.76 (dd, J=8.7 Hz, 4H), 5.15 (s, 2H), 2.76 (d, J=4.8 Hz, 3H); MS (ESI) m/z: 244 (M+H+).

Provenance & Evidence