3,3,5,5-Tetramethylcyclohexanone → HCID 11992475, compound

Participants

Reaction Steps

To a stirred suspension of Zn (0.59 g, 8.94 mmol) in THF (10 mL) was added TiCl4 (0.50 mL, 4.47 mmol) dropwise. The mixture was refluxed under nitrogen for 2.5 h. Cooled to room temperature, a solution of 7 (0.32 g, 1.12 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.53 g, 3.35 mmol) in THF (15 mL) was added and the reaction mixture was refluxed for another 2.5 h. Cooled 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 combined organic extracts were washed with brine, dried (Na2SO4) and concentrated to a pale yellow oil. The residue was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 45% EtOAc:hexanes to give 8 as a white solid. Crystallization from 10:1 hexanes:EtOAc yielded colorless needles (0.27 g, 59%). mp 116-117° C. 1H NMR (400 MHz, CD3OD): δ0.91 (s, 6H), 0.93 (s, 6H), 1.29 (s, 2H), 1.95 (s, 2H), 1.99 (s, 2H), 3.60-3.65 (m, 2H), 3.65-3.70 (m, 2H), 3.80-3.85 (m, 2H), 4.05-4.15 (m, 2H), 6.85 (d, J=8.6 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.10-7.20 (m, 3H), 7.20-7.30 (m, 2H). LRMS (ESI): m/z 409 (M+H)+. Anal. Calcd for C27H36O3: C, 79.37; H, 8.88. Found: C, 79.23; H, 8.95.

Provenance & Evidence