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

Temperature

0 °C

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).

1. customthe reaction was sonicated for 30 seconds during which time a deep red color
2. customformed
3. temperatureto warm to room temperature
4. stirringstirred for 1.5 hours
5. temperatureto warm to room temperature
6. stirringstirred for 1 hour
7. washThe reaction was washed with water (50 mL), saturated aqueous sodium chloride (50 mL)
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customThe residue was purified by flash chromatography (Biotage) over silica gel eluting with hexane/ethyl acetate (50:1)

ORD record

ord-e685293a622b47edb7724bb3f2c6cc1c

Source dataset

uspto-grants-2002_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06420418B1