Potassium Iodide → 4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

Participants

Reaction Steps

3-(chloromethyl)-1-isopropylazetidine hydrochloride (2.8 g, 15.2 mmol), 4-(4-hydroxyphenyl)tetrahydropyran-4-carbonitrile (3.1 g, 15.2 mmol) and potassium carbonate (8.5 g, 61.6 mmol) were combined in DMF (40 ml) and stirred at 500 for 2 hours. Potassium iodide (0.5 g 3.0 mmol) was added and the mixture was stirred at 50° for 18 hours then at 90-95° for a further 5 hours. The reaction mixture was concentrated in vacuo then partitioned between ethyl acetate (80 ml) and water (50 ml). The ethyl acetate was washed with saturated NaCl (50 ml) then dried over Na2SO4 and concentrated in vacuo to give a brown semi-crystalline material which was triturated with diisopropyl ether (25 ml) to give the title compound as a beige powder (2.9 g, 60%). 1H NMR (400 MHz, CDCl3) δ7.38 (d, 2H), 6.91 (d, 2H), 4.08 (m, 4H), 3.89 (m, 2H), 3.41 (t, 2H), 3.02 (t, 2H), 2.87 (m, 1H), 2.31 (m, 1H), 2.15-2.00 (m, 4H), 0.94 (d, 6H).

Provenance & Evidence