Cesium fluoride → 1-(2-(4-(6-Methoxy-2-(thiophen-2-yl)naphthalen-1-yloxy)phenoxy)ethyl)piperidine

Participants

Reaction Conditions

Reaction Steps

Combine 6-methoxy-1-(4-(2-(piperidin-1-yl)ethoxy)phenoxy)naphthalen-2-yl trifluoromethanesulfonate (6.0 g, 11.4 mmol), Thiophene-2-boronic Acid (4.4 g, 34.3 mmol), tricyclohexylphosphine (1.1 g, 4.0 mmol), palladium (II) acetate (0.51 g, 2.3 mmol), cesium fluoride (15.6 g, 102.8 mmol) and acetonitrile (150 mL; degas with nitrogen for 30 minutes) to a round bottom flask under nitrogen. Warm the resulting mixture to 80° C. and stir for 40 minutes. Filter off solids and wash with acetonitrile. Combine the filtrate and washes and concentrate in vacuo. Dissolve the residue in methanol and load onto an SCX acidic ion exchange column. Flush the column with methanol then elute with 2M ammonia in methanol. Concentrate the ammonia containing eluent in vacuo to give a light brown solid. Purify the solid by silica gel flash chromatography to obtain the title compound (3.88 g, 8.4 mmol). 1H NMR (d6-DMSO) δ29 (dd, J=5.9, 11.2 Hz, 2H), 1.43-1.37 (m, 5H), 2.32 (s, 4H), 2.52 (t, J=5.9 Hz, 2H), 3.87 (t, J=6.1 Hz, 2H), 6.62-6.60 (m, 2H), 6.76-6.74 (m, 2H), 7.09-7.03 (m, 2H), 7.37 (d, J=2.6 Hz, 1H), 7.48-7.47 (m, 1H), 7.62-7.59 (m, 2H), 7.76 (d, J=8.8 Hz, 1H), 7.96 (d, J=8.8 Hz, 1H).

Provenance & Evidence