Bromide ion → Isohexane ethyl acetate

Participants

Reaction Steps

5-Bromo-2-fluoro-benzotrifluoride (3.16 g, 13 mmol) was added over 5-10 minutes as a solution in diethyl ether (14 mL in total) dropwise to magnesium turnings (0.316 g, 13 mmol) in diethyl ether (1 mL), under an atmosphere of nitrogen. The reaction was maintained at a gentle reflux by control of addition rate during addition of the bromide and then allowed to cool to room temperature and stirred for a further 1 hr. Copper (I) iodide (206 mg, 1.08 mmol) was added in one portion and the reaction mixture cooled to 0° C. over 10 minutes. (R)-epichlorohydrin (1.0 g, 10.8 mmol) was added as a solution in diethyl ether (14 mL in total) over 10 minutes and the reaction allowed to warm to room temperature and stirred for 2 hrs. Ammonium chloride (saturated aqueous solution, 10 mL) and the mixture poured into water (40 mL) and extracted with ethyl acetate (30 mL×2). The combined organic layers were washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. Column chromatography (silica; 5% ethyl acetate/isohexane) yielded the desired intermediate (d), (R)-1-chloro-3-(4-fluoro-3-trifluoromethylphenyl)-2-propanol, as a pale yellow oil (3.75 g).

Provenance & Evidence