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

A solution of 4-aminophenol (9.60 g, 88.0 mmol) in anhydrous DMF (150 mL) was treated with potassium tert-butoxide (10.29 g, 91.7 mmol), and the reddish-brown mixture was stirred at RT for 2 h. The contents were treated with 4-chloropyridine-2-carboxylic acid methylamide (15.0 g, 87.9 mmol) and K2CO3 (6.50 g, 47.0 mmol) and then heated at 80° C. for 8 h. The mixture was cooled to RT and partitioned between EtOAc (500 mL) and a saturated NaCl solution (500 mL). The aqueous phase was back-extracted with EtOAc (300 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The resulting solids were dried under reduced pressure at 35° C. for 3 h to afford the title compound (17.9 g, 84%) as a light-brown solid. 1H-NMR (DMSO-d6) δ 2.77 (d, J=4.8 Hz, 3H), 5.17 (br s, 2H), 6.64, 6.86 (AA′BB′ quartet, J=8.4 Hz, 4H), 7.06 (dd, J=5.5, 2.5 Hz, 1H), 7.33 (d, J=2.5 Hz, 1H), 8.44 (d, J=5.5 Hz, 1H), 8.73 (br d, 1H); HPLC ES-MS m/z 244 (MH+).

1. temperatureheated at 80° C. for 8 h
2. temperatureThe mixture was cooled to RT
3. custompartitioned between EtOAc (500 mL)
4. extractionThe aqueous phase was back-extracted with EtOAc (300 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customThe resulting solids were dried under reduced pressure at 35° C. for 3 h

ORD record

ord-d1b5e96aa64a40e781967a623f7e5d32

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08076488B2