Cycloheptanone → 4-[(4-Bromo-3-fluorophenyl)(cycloheptylidene)methyl]phenol

Participants

Reaction Steps

To a stirred suspension of zinc powder (0.90 g, 13.8 mmoL) in anhydrous THF (20 mL) was slowly added TiCl4 (0.75 mL, 1.3 g, 6.8 mmoL) via syringe at RT under a nitrogen atmosphere. (Note: significant fuming occurred upon addition of TiCl4.) The reaction mixture was heated at reflux with stirring under nitrogen for 2.25 h. A solution of (4-bromo-3-fluorophenyl)(4-hydroxyphenyl)methanone (186) (0.50 g, 1.7 mmoL) and cycloheptanone (0.6 mL, 0.57 g, 5.09 mmoL) in THF (10 mL) was added to the reaction mixture via syringe. The reaction mixture was heated at reflux for 2 h. The oil bath was removed and the reaction mixture was allowed to cool at RT. To the reaction mixture was added H2O (10 mL) followed by 10% K2CO3 (10 mL). The quenched reaction mixture was filtered through a pad of Celite with the aid of EtOAc and H2O. The pad was washed with EtOAc and the filtrate was transferred to a separatory funnel. The layers were separated and the organic phase was allowed to stand at RT over the weekend. The organic phase was dried over MgSO4, filtered, and the filtrate was concentrated in vacuo to give the crude product. The crude product was purified by flash chromatography on silica gel with a hexanes:EtOAc gradient (100:0 to 50:50) to give 0.48 g (75%) of compound 187 as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ 1.50 (m, 8H), 2.20 (m, 4H), 6.67 (d, J=8.4 Hz, 2H), 6.88 (dd, J=1.9 Hz, 8.3 Hz, 1H), 6.92 (d, J=8.4 Hz, 2H), 7.08 (dd, J=1.8 Hz, 10.0 Hz, 1H), 7.59 (t, J=7.9 Hz, 1H), 9.33 (s, 1H). LRMS (ESI): m/z 373 (M−H)−.

Provenance & Evidence