3,3,5,5-Tetramethylcyclohexanone → 2-({4-[Phenyl(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}oxy)ethanol

Participants

Reaction Steps

To a stirred suspension of Zn (0.65 g, 9.91 mmol) in THF (10 mL) was added TiCl4 (0.55 mL, 4.95 mmol) dropwise. The mixture was refluxed under nitrogen for 2.5 h. After cooling to room temperature, a solution of 5 (0.30 g, 1.24 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.59 g, 3.71 mmol) in THF (17 mL) was added at once. The reaction mixture was refluxed for another 2.5 h. Following cooling to room temperature, the reaction was quenched with 10% K2CO3 (40 mL). The quenched reaction mixture was filtered through a pad of celite and the pad was washed with EtOAc (100 mL). The filtrate was transferred to a separatory funnel, the layers were separated, and the aqueous layer was extracted with EtOAc (50 mL). The organic extracts were combined, washed with brine, dried (Na2SO4) and concentrated to give a pale yellow oil. The residue was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 20% EtOAc:hexanes to give 6 as a white solid (0.35 g, 78%). mp 131-132° C. 1H NMR (400 MHz, CD3OD): δ 0.91 (s, 6H), 0.92 (s, 6H), 1.29 (s, 2H), 1.95 (s, 2H), 1.99 (s, 2H), 3.80-3.85 (m, 2H), 4.00-4.05 (m, 2H), 6.85 (d, J=8.8 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.10-7.20 (m, 3H), 7.20-7.25 (m, 2H). LRMS (ESI): m/z 365 (M+H)+. Anal. Calcd for C25H32O2: C, 82.37; H, 8.85. Found: C, 82.11; H, 9.03.

Provenance & Evidence