Benzene, 1-bromo-3-(trifluoromethyl)- → 4-Chloro-1-[4-(trifluoromethyl)phenyl]butan-1-one

Participants

Reaction Conditions

Reaction Steps

Magnesium metal (0.6 g, 24.4 mmol) was placed into a 25 mL round bottomed flask and was vigorously stirred under nitrogen for 24 hours. To this activated magnesium was added 1 mL of tetrahydrofuran and 4-bromobenzotrifluoride (0.5 g, 2.2 mmol) and the reaction was sonicated for 30 seconds during which time a deep red color formed. The solution was cooled to 0° C. and 3-bromobenzotrifluoride (4.5 g, 20 mmol) in 9 mL of tetrahydrofuran was added dropwise. The reaction was allowed to warm to room temperature and stirred for 1.5 hours then added to a solution of 4-chlorobutyryl chloride (9.4 g, 66.6 mmol) in 50 mL of tetrahydrofuran at −78° C. The reaction was allowed to warm to room temperature and stirred for 1 hour. The reaction was washed with water (50 mL), saturated aqueous sodium chloride (50 mL), dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography (Biotage) over silica gel eluting with hexane/ethyl acetate (50:1) to give 2.3 g of the title compound as an oil. 1H NMR (500 MHz, CDCl3): δ 8.08 (d, 2H, J=8.3 Hz); 7.74 (d, 2H, J=8.0 Hz); 3.69 (m, 2H); 3.21 (m, 2H); 2.25 (m, 2H).

Provenance & Evidence