Uses
1-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanone can be used as a pesticide intermediate, mainly in the synthesis of sarolaner.
Synthesis
The general procedure for the synthesis of 3,5-dichloro-4-fluorotrifluoroacetylbenzene from 1-trifluoroacetylpiperidine and 3,5-dichloro-4-fluorobromobenzene is as follows:
Intermediate 3: Synthesis of 1-(4-chloro-3,5-difluorophenyl)-2,2,2-trifluoroacetophenone
1. 5-bromo-2-fluoro-1,3-dichlorobenzene (7.0 g, 28.7 mmol) was dissolved in THF (50 mL) under argon protection and stirred at room temperature.
2. isopropylmagnesium chloride lithium chloride complex (24.3 mL, 1.3 M solution in THF, 1.1 equiv) was added slowly over 1 min and stirring was continued at room temperature for 30 min.
3. The reaction system was cooled to 0 °C and piperidine trifluoroacetamide (5.6 mL, 1.32 equiv.) was added over about 1 min.
4. The reaction mixture was stirred at room temperature for 2 hours.
5. Upon completion of the reaction, the reaction was quenched with saturated aqueous NH4Cl solution (50 mL).
6. The reaction mixture was extracted with methyl tert-butyl ether (MTBE, 2 x 50 mL).
7. The organic phases were combined and concentrated under reduced pressure to remove the solvent.
8. The crude product was purified by chromatography on a 12 g Redi-Sep column with the eluent being a heptane solution of 0 to 50% ethyl acetate to give 3.5 g of 1-(4-chloro-3,5-difluorophenyl)-2,2,2-trifluoroethanone.
Product Characterization:
1H-NMR (400 MHz, CDCl3) δ ppm 8.06 (dd, 2H, J1 = 6.2 Hz, J2 = 0.9 Hz).
