ethyl 4,4,4-trifluoro-3-methylbutanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-di-cyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly, and the reaction solution was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methyl-butanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC, mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly to the reaction solution, and the mixture was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly to the reaction solution, and the mixture was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-di-cyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly, and the reaction solution was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methyl-butanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC, mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were added slowly, and the reaction solution was then stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to RT and then heated to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to RT and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to RT heated to 80° C The mixture was stirred at this temperature for 2 h cooled to RT stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were added slowly, and the reaction solution was then stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to RT and then heated to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to RT and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to RT heated to 80° C The mixture was stirred at this temperature for 2 h cooled to RT stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were added slowly, and the reaction solution was then stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to RT and then heated to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to RT and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to RT heated to 80° C The mixture was stirred at this temperature for 2 h cooled to RT stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly, and the reaction solution was stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed initially to RT and then to 80° C. The mixture was stirred at this temperature for 2 h, then cooled to RT and stirred overnight. After the reaction had gone to completion (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid. The reaction solution was then cooled to −10° C. were then added dropwise the reaction solution was warmed initially to RT to 80° C The mixture was stirred at this temperature for 2 h cooled to RT stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were added slowly, and the reaction solution was then stirred at RT for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to RT and then heated to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to RT and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kiesel-guhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colourless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to RT heated to 80° C The mixture was stirred at this temperature for 2 h cooled to RT stirred overnight the reaction mixture was filtered through kiesel-guhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, a solution of 1.29 g (7.02 mmol) of (+/−)-ethyl 4,4,4-trifluoro-3-methylbutanoate in 2 ml of abs. toluene was added dropwise to 8.1 ml of a 1 M solution, cooled to −10° C., of lithium hexamethyldisilazide in toluene (8.1 mmol). After 10 min at −10° C., a mixture of 1.0 g (5.4 mmol) of 1-bromo-4-ethylbenzene, 36.4 mg (0.16 mmol) of palladium(II) acetate and 134 mg (0.34 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl in 5 ml of abs. toluene was added to this reaction mixture. After the addition had ended, the mixture was warmed to RT and then stirred first at RT for 1 h and then at 80° C. for a further 3 h. After cooling to RT, the precipitated salts were filtered off with suction, the residue was washed with toluene and the combined filtrates were concentrated under reduced pressure. This gave 1.26 g of crude product (80.9% of theory) which was reacted as such. After the addition at 80° C. for a further 3 h After cooling to RT the precipitated salts were filtered off with suction the residue was washed with toluene the combined filtrates were concentrated under reduced pressure This gave 1.26 g of crude product (80.9% of theory) which was reacted as such

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly to the reaction solution, and the mixture was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methylbutanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC; mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as a colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under argon, 196.9 mg (0.88 mmol) of palladium(II) acetate and 724.8 mg (1.84 mmol) of 2-di-cyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl were initially charged in 50 ml of anhydrous toluene. 43.8 ml (43.8 mmol) of a 1 M solution of lithium hexamethyldisilazide in THF were then added slowly, and the reaction solution was stirred at room temperature for 10 min. The reaction solution was then cooled to −10° C., 7 g (38.0 mmol) of ethyl 4,4,4-trifluoro-3-methyl-butanoate were added slowly and the mixture was stirred at −10° C. for 10 min. 5 g (29.2 mmol) of 4-bromotoluene, dissolved in 50 ml of toluene, were then added dropwise, and the reaction solution was warmed first to room temperature and then to 80° C. The mixture was stirred at this temperature for 2 h and then cooled to room temperature and stirred overnight. After the reaction had ended (monitored by TLC, mobile phase cyclohexane/dichloromethane 2:1), the reaction mixture was filtered through kieselguhr, the residue was washed repeatedly with ethyl acetate and dichloromethane and the combined filtrates were concentrated under reduced pressure. The crude product obtained was purified chromatographically on silica gel (mobile phase petroleum ether/dichloromethane 4:1→3:1). This gave 3.91 g (14.3 mmol, 48.8% of theory) of the title compound as colorless liquid. The reaction solution was then cooled to −10° C. the mixture was stirred at −10° C. for 10 min were then added dropwise the reaction solution was warmed first to room temperature to 80° C The mixture was stirred at this temperature for 2 h cooled to room temperature stirred overnight the reaction mixture was filtered through kieselguhr the residue was washed repeatedly with ethyl acetate and dichloromethane the combined filtrates were concentrated under reduced pressure