Sodium Iodide → HCID 67513491, compound

Participants

Reaction Steps

To a solution of 4-(4-methoxyphenyl)cyclohexanone (INTERMEDIATE 7, Step A) (219.6 mg, 1.075 mmol) in DCM (5 ml), under nitrogen at 0° C., was added hexamethyldisilazane (0.272 ml, 1.290 mmol) followed by dropwise addition of iodotrimethylsilane (0.161 ml, 1.183 mmol). A solution of sodium iodide (161 mg, 1.075 mmol) in THF (3.3 ml) was then added, followed by addition of a cloudy mixture of m-CPBA (318 mg, 1.290 mmol) in DCM (3 ml). At 10 minutes, added ethyl acetate and washed with 1M aqueous hydrochloric acid (added brine to help break emulsion). The aqueous layer was extracted with EtOAc and the combined organics were washed with saturated aqueous sodium thiosulfate, followed by saturated aqueous sodium bicarbonate, and brine. The organic layer was dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc in hexanes to afford each diastereomer of the titled compound. Either one can be used on Step B. 1H NMR (500 MHz, CDCl3) (trans): δ 7.19-7.14 (m, 2H); 6.90-6.85 (m, 2H); 4.73-4.71 (m, 1H); 3.80 (s, 3H); 3.54 (td, J=14.6, 6.2 Hz, 1H); 3.46-3.40 (m, 1H); 2.42-2.37 (m, 1H); 2.30-2.25 (m, 1H); 2.23-2.09 (m, 2H); 1.93 (qd, J=13.3, 4.2 Hz, 1H). 1H NMR (500 MHz, CDCl3) (cis): δ 7.16-7.11 (m, 2H); 6.88-6.83 (m, 2H); 5.05 (dd, J=13.5, 5.9 Hz, 1H); 3.78 (s, 3H); 3.12-3.08 (m, 1H); 2.88-2.77 (m, 2H); 2.68 (dd, J=14.1, 6.1 Hz, 1H); 2.48 (q, J=12.9 Hz, 1H); 2.29-2.25 (m, 1H); 1.98 (dd, J=13.2, 4.4 Hz, 1H).

Provenance & Evidence