3',5'-DICHLORO-2,2,2-TRIFLUOROACETOPHENONE,C8H3Cl2F3O,CAS 130336-16-2

Under a nitrogen atmosphere, tert-butyllithium (1.3 Msolution in Pentane, 17.8 mL, 23.2 mmol) was added dropwise to a solution of 3, 5-dichlorobenzene (5.0 g, 22.1mmol) in tetrahydrofuran (50 mL) for 30 min and the reaction was continued for 2 hours. Trifluoroacetic anhydride is then added(2.56 g, 12.2 mmol) was added dropwise to the mixed solution and stirring was continued for 2 hours while maintaining at -78 ° C. Remove the cold, gradually rose toAfter room temperature, keep the reaction at room temperature for 2.5 hours. Saturated ammonium chloride solution (50 mL) was added to terminate the reaction. The mixture was extracted with etherThe organic phase was combined and washed with saturated brine (20 mL'2). The organic phase was separated and washed with anhydrous magnesium sulfateDrying, filtration, removal of the solvent, and distillation under reduced pressure gave a colorless transparent liquid 1 (2.58 g) in a yield of 48percent.Example S.3: Synthesis of 3, 5-dichloro-2, 2, 2-trifluoro acetophenone (Compound example no.2 of table C.1 ); To 5.1 g (0.209 mol) Magnesium turnings was added 0.45 g of a 1 molar solution of DIBAL in hexane at 6OUnder a nitrogen atmosphere, tert-butyllithium (1.3 Msolution in Pentane, 17.8 mL, 23.2 mmol) was added dropwise to a solution of 3, 5-dichlorobromobenzene (5.0 g, 22.1 mmol) in tetrahydrofuran (50 mL) dropwise over 30 min. The mixture was stirred for 2 hours and then N-methoxy-N-Methyl-2, 2, 2-trifluoroacetamide (3.64 g, 23.2 mmol) was added dropwise to the mixed solution, the reaction 2 was stirred while maintaining -78 ° Chour. Remove the low temperature, the temperature gradually rose to room temperature, the reaction was maintained at room temperature for 8 hours. Saturated ammonium chloride solution (50 mL)The reaction was quenched and extracted with ether (20 mL & apos; 3). The organic phases were combined and washed with brine (20 mL & apos; 2)The phases were dried over anhydrous magnesium sulfate, filtered, the solvent was removed and the residue was distilled under reduced pressure to give a colorless transparent liquid 1 (1.56 g). Yield29percent.Step 1 Method B. l-(3, 5-Dichlorophenyl)-2, 2, 2-trifluoroethanol (AI2). To a stirred solution of 3, 5-dichlorobenzaldehyde (10 g, 57 mmol) in tetrahydrofuran (THF; 250 mL) were added trifluoromethyltrimethylsilane (9.79 g, 69.2 mmol) and a catalytic amount of tetrabutylammonium fluoride (TBAF). The reaction mixture was stirred at 25 °C for 8 h. After the reaction was deemed complete by TLC, the reaction mixture was diluted with 3 N hydrochloric acid (HCl) and then was stirred for 16 h. The reaction mixture was diluted with HExample S.3: Synthesis of 3, 5-dichloro-2, 2, 2-trifluoro acetophenone (Compound example no.2 of table C.1 ); To 5.1 g (0.209 mol) Magnesium turnings was added 0.45 g of a 1 molar solution of DIBAL in hexane at 6OExample S.3: Synthesis of 3, 5-dichloro-2, 2, 2-trifluoro acetophenone (Compound example no.2 of table C.1 ); To 5.1 g (0.209 mol) Magnesium turnings was added 0.45 g of a 1 molar solution of DIBAL in hexane at 6OUnder a nitrogen atmosphere, tert-butyllithium (1.3 Msolution in Pentane, 17.8 mL, 23.2 mmol) was added dropwise to a solution of 3, 5-dichlorobenzene (5.0 g, 22.1mmol) in tetrahydrofuran (50 mL) dropwise over 30 min and stirring was continued for 2 h. Then 1-trifluoroacetyl piperidine(4.20 g, 23.2 mmol) was added dropwise to the mixed solution, and the reaction was stirred and maintained at -78 ° C for 2 hours. Remove low temperature and gradually rise to roomAfter the temperature, keep the reaction at room temperature for 6 hours. The reaction was quenched by addition of saturated ammonium chloride solution (50 mL). The mixture was extracted with ether(20 mL '3). The organic phases were combined and washed with saturated brine (20 mL' 2). The organic phase was separated and dried over anhydrous magnesium sulfateDrying, filtration, removal of solvent, and distillation under reduced pressure gave colorless transparent liquid 1 (2.09 g) in 39percent yield.Example S.3: Synthesis of 3, 5-dichloro-2, 2, 2-trifluoro acetophenone (Compound example no.2 of table C.1 ); To 5.1 g (0.209 mol) Magnesium turnings was added 0.45 g of a 1 molar solution of DIBAL in hexane at 6OUnder a nitrogen atmosphere, tert-butyllithium (1.3 Msolution in Pentane, 17.8 mL, 23.2 mmol) was added dropwise to a solution of 3, 5-dichlorobenzene (5.0 g, 22.1mmol) in tetrahydrofuran (50 mL) over 30 min. The mixture was stirred for further 2 hours. Then threeEthyl fluoroacetate (3.30 g, 23.2 mmol) was added dropwise to the mixed solution, and the reaction was stirred for 2 hours while maintaining at -78 ° C. Remove low temperature, After gradually rising to room temperature, the reaction was kept at room temperature for 4 hours. The reaction was quenched by addition of saturated ammonium chloride solution (50 mL). Mixed solution usedThe organic phase was combined and washed with saturated brine (20 mL'2). The organic phase was separated and washed with waterDry over magnesium sulfate, filter and remove solvent. Vacuum distillation gave a colorless transparent liquid 1 (2.20 g), yield 41percent.