Morpholine → 4-(2-Fluoro-4-nitrophenyl)morpholine

Participants

Reaction Steps

In a 250 ml 3-neck round bottom flask with mechanical stirrer, septum and drying tube was added 3,4-difluoronitrobenzene (1) (12.91 g, 81.1 mmol), methanol (60 ml) and morpholine (15.93 g, 16 ml, 183 mmol). The clear solution was heated at reflux with stirring for 2 hours. The reaction mixture containing yellow crystals was cooled in an ice bath for 1 hour with stirring. The crystals were collected by filtration and dried in vacuo (1 mm) at room temperature for 3 hours (16.99 g, 93%). Homogenous by TLC (silica gel, CHCl3) Rf=0.54 (yellow spot) 1H NMR (500 MHz, CDCl3) δ 8.00 (ddd, 1H, J=9 Hz, J=2.6 Hz, J=1 Hz), 7.92 (dd, 1H, J=13.1 Hz, J=2.5 Hz,), 6.92 (dd, 1H, J=8.8 Hz, J=8.8 Hz), 3.86 (dd, 4H, J=4.7 Hz, J=4.7 Hz), 3.28 (dd, 4H, J=4.7 Hz, J=4.7 Hz). LCMS (Method A) 0.79 min m/e 227.

Provenance & Evidence