Epichlorohydrin → 1-Chloro-3-(3-fluoro-2-methyl-phenyl)-propan-2-ol

Participants

Reaction Steps

0.867 g (35.67 mmol) of magnesium turnings were dried and suspended in 17 ml of anhydrous THF under argon. A solution of 1,2-dibromoethane (0.14 ml, 1.62 mmol) and 2-bromo-6-fluoro-toluene (6.74 g, 35.67 mmol) in 17 ml of anhydrous THF was then added dropwise so as to maintain a gentle reflux. Once the magnesium had been consumed, copper(I) iodide (0.432 g, 2.27 mmol) was then added, followed by a solution of epichlorohydrine (3.00 g, 32.42 mmol) in DMF (8 ml). The mixture was stirred for 3.5 h at room temperature and then quenched with a saturated solution of ammonium chloride (120 ml). The organic layer was separated, and the aqueous phase was extracted twice with EA. The combined organic phases were washed twice with a saturated solution of ammonium chloride, dried over sodium sulfate, filtered and evaporated to dryness. The product was purified by chromatography on silica gel (cyclohexane/EA, from 100:0 to 90:10) to give 6.89 g of 1-chloro-3-(3-fluoro-2-methyl-phenyl)-propan-2-ol. 3.92 g (16.23 mmol) of this alcohol were dissolved in DCM under argon, and 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane reagent; 7.57 g, 16.23 mmol) was added. The mixture was stirred at room temperature overnight and then diethyl ether (150 ml) was added. The mixture was washed three times with 1 N hydrochloric acid (70 ml) and twice with a saturated solution of sodium chloride, and extracted with ether. The extracts were dried over sodium sulfate, filtered and evaporated to dryness. 2.69 g of the title compound were obtained as a white powder.

Provenance & Evidence