1-(3-bromophenyl)-2,2,2-trifluoroethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon and with stirring, 22.7 ml (22.7 mmol) of a 1 M solution of methylmagnesium bromide in diethyl ether were added dropwise at 0° C. to a solution of 5.22 g (20.6 mmol) of 1-(3-bromophenyl)-2,2,2-trifluoroethanone in 40 ml of anhydrous THF. After the addition had ended, the reaction mixture was stirred at 0° C. for another 30 min. Then—still at 0° C.—excess Grignard reagent was hydrolyzed by careful addition of water. The mixture was then adjusted to a pH of about 5 by addition of 2 M hydrochloric acid. The phases were separated and the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether. The combined organic phases were dried over magnesium sulphate, filtered and evaporated to dryness on a rotary evaporator. This gave 5.32 g (95% of theory) of the title compound. After the addition the reaction mixture was stirred at 0° C. for another 30 min The phases were separated the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether The combined organic phases were dried over magnesium sulphate filtered evaporated to dryness on a rotary evaporator

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon and with stirring, 22.7 ml (22.7 mmol) of a 1 M solution of methylmagnesium bromide in diethyl ether were added dropwise at 0° C. to a solution of 5.22 g (20.6 mmol) of 1-(3-bromophenyl)-2,2,2-trifluoroethanone in 40 ml of anhydrous THF. After the addition had ended, the reaction mixture was stirred at 0° C. for another 30 min. Then—still at 0° C.—excess Grignard reagent was hydrolyzed by careful addition of water. The mixture was then adjusted to a pH of about 5 by addition of 2 M hydrochloric acid. The phases were separated and the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether. The combined organic phases were dried over magnesium sulphate, filtered and evaporated to dryness on a rotary evaporator. This gave 5.32 g (95% of theory) of the title compound. After the addition the reaction mixture was stirred at 0° C. for another 30 min The phases were separated the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether The combined organic phases were dried over magnesium sulphate filtered evaporated to dryness on a rotary evaporator

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an oven-dried round bottom flask fitted with a stir bar and a rubber septum was added 1-(3-bromo-phenyl)-2,2,2-trifluoro-ethanone (560 mg, 2.2 mmol, as prepared in Example 28, step a), 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.96 mL, 6.6 mmol, Aldrich Chemical Company), (PPh3)2PdCl2 (93 mg, 0.132 mmol, Strem Chemicals, Inc., Newburyport, Mass.), and Et3N (1.8 mL, 13.2 mmol). The reaction mixture was evacuated, purged with argon, and then suspended in dioxane (16 mL). After stirring for 18 hr at 95° C., the reaction was allowed to cool and then filtered through Celite.® The filtrate was concentrated in vacuo and the residue was purified by chromatography (SiO2, flash elution: 5% EtOAc in hexanes) to give 350 mg (53%) of an oil that was used without further purification. To an oven-dried round bottom flask fitted with a stir bar The reaction mixture was evacuated purged with argon to cool filtered through Celite ® The filtrate was concentrated in vacuo the residue was purified by chromatography (SiO2, flash elution: 5% EtOAc in hexanes)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottom flask, 3-bromo-benzoic acid methyl ester (2 g, 9.3 mmol, Aldrich Chemical Company) and trimethyl(trifluoromethyl)silane (1.72 mL, 11.6 mmol, Aldrich Chemical Company) were dissolved in dry toluene (50 mL). Upon cooling the solution to −78° C., TBAF (232 μL, 0.23 mmol) was added and the reaction was allowed to warm up slowly to rt overnight. After stirring for 20 hr, 2N HCl (50 mL) and EtOAc (100 mL) were added, the layers were separated, and the aqueous layer was extracted with another portion of EtOAc. The combined organic fractions were dried (MgSO4), concentrated in vacuo, and resulting crude oil was purified using SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes) to give 1.5 g (65%) the title compound as a light yellow oil. 1H-NMR (CDCl3; 400 MHz) δ 8.18 (br s, 1H), 7.98–8.00 (m, 1H), 7.82–7.85 (m, 1H), 7.42–7.46 (m, 1H). 19F-NMR (CDCl3; 400 MHz) δ −72.06 (s). to warm up slowly to rt overnight the layers were separated the aqueous layer was extracted with another portion of EtOAc The combined organic fractions were dried (MgSO4) concentrated in vacuo resulting crude oil was purified SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottom flask, 3-bromo-benzoic acid methyl ester (2 g, 9.3 mmol, Aldrich Chemical Company) and trimethyl(trifluoromethyl)silane (1.72 mL, 11.6 mmol, Aldrich Chemical Company) were dissolved in dry toluene (50 mL). Upon cooling the solution to −78° C., TBAF (232 μL, 0.23 mmol) was added and the reaction was allowed to warm up slowly to rt overnight. After stirring for 20 hr, 2N HCl (50 mL) and EtOAc (100 mL) were added, the layers were separated, and the aqueous layer was extracted with another portion of EtOAc. The combined organic fractions were dried (MgSO4), concentrated in vacuo, and resulting crude oil was purified using SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes) to give 1.5 g (65%) the title compound as a light yellow oil. 1H-NMR (CDCl3; 400 MHz) δ 8.18 (br s, 1H), 7.98–8.00 (m, 1H), 7.82–7.85 (m, 1H), 7.42–7.46 (m, 1H). 19F-NMR (CDCl3; 400 MHz) δ −72.06 (s). to warm up slowly to rt overnight the layers were separated the aqueous layer was extracted with another portion of EtOAc The combined organic fractions were dried (MgSO4) concentrated in vacuo resulting crude oil was purified SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an oven-dried round bottom flask fitted with a stir bar and a rubber septum was added 1-(3-bromo-phenyl)-2,2,2-trifluoro-ethanone (560 mg, 2.2 mmol, as prepared in Example 28, step a), 4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (0.96 mL, 6.6 mmol, Aldrich Chemical Company), (PPh3)2PdCl2 (93 mg, 0.132 mmol, Strem Chemicals, Inc., Newburyport, Mass.), and Et3N (1.8 mL, 13.2 mmol). The reaction mixture was evacuated, purged with argon, and then suspended in dioxane (16 mL). After stirring for 18 hr at 95° C., the reaction was allowed to cool and then filtered through Celite.® The filtrate was concentrated in vacuo and the residue was purified by chromatography (SiO2, flash elution: 5% EtOAc in hexanes) to give 350 mg (53%) of an oil that was used without further purification. To an oven-dried round bottom flask fitted with a stir bar The reaction mixture was evacuated purged with argon to cool filtered through Celite ® The filtrate was concentrated in vacuo the residue was purified by chromatography (SiO2, flash elution: 5% EtOAc in hexanes)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottom flask, 3-bromo-benzoic acid methyl ester (2 g, 9.3 mmol, Aldrich Chemical Company) and trimethyl(trifluoromethyl)silane (1.72 mL, 11.6 mmol, Aldrich Chemical Company) were dissolved in dry toluene (50 mL). Upon cooling the solution to −78° C., TBAF (232 μL, 0.23 mmol) was added and the reaction was allowed to warm up slowly to rt overnight. After stirring for 20 hr, 2N HCl (50 mL) and EtOAc (100 mL) were added, the layers were separated, and the aqueous layer was extracted with another portion of EtOAc. The combined organic fractions were dried (MgSO4), concentrated in vacuo, and resulting crude oil was purified using SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes) to give 1.5 g (65%) the title compound as a light yellow oil. 1H-NMR (CDCl3; 400 MHz) δ 8.18 (br s, 1H), 7.98–8.00 (m, 1H), 7.82–7.85 (m, 1H), 7.42–7.46 (m, 1H). 19F-NMR (CDCl3; 400 MHz) δ −72.06 (s). to warm up slowly to rt overnight the layers were separated the aqueous layer was extracted with another portion of EtOAc The combined organic fractions were dried (MgSO4) concentrated in vacuo resulting crude oil was purified SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottom flask, 3-bromo-benzoic acid methyl ester (2 g, 9.3 mmol, Aldrich Chemical Company) and trimethyl(trifluoromethyl)silane (1.72 mL, 11.6 mmol, Aldrich Chemical Company) were dissolved in dry toluene (50 mL). Upon cooling the solution to −78° C., TBAF (232 μL, 0.23 mmol) was added and the reaction was allowed to warm up slowly to rt overnight. After stirring for 20 hr, 2N HCl (50 mL) and EtOAc (100 mL) were added, the layers were separated, and the aqueous layer was extracted with another portion of EtOAc. The combined organic fractions were dried (MgSO4), concentrated in vacuo, and resulting crude oil was purified using SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes) to give 1.5 g (65%) the title compound as a light yellow oil. 1H-NMR (CDCl3; 400 MHz) δ 8.18 (br s, 1H), 7.98–8.00 (m, 1H), 7.82–7.85 (m, 1H), 7.42–7.46 (m, 1H). 19F-NMR (CDCl3; 400 MHz) δ −72.06 (s). to warm up slowly to rt overnight the layers were separated the aqueous layer was extracted with another portion of EtOAc The combined organic fractions were dried (MgSO4) concentrated in vacuo resulting crude oil was purified SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a dry round bottom flask, 3-bromo-benzoic acid methyl ester (2 g, 9.3 mmol, Aldrich Chemical Company) and trimethyl(trifluoromethyl)silane (1.72 mL, 11.6 mmol, Aldrich Chemical Company) were dissolved in dry toluene (50 mL). Upon cooling the solution to −78° C., TBAF (232 μL, 0.23 mmol) was added and the reaction was allowed to warm up slowly to rt overnight. After stirring for 20 hr, 2N HCl (50 mL) and EtOAc (100 mL) were added, the layers were separated, and the aqueous layer was extracted with another portion of EtOAc. The combined organic fractions were dried (MgSO4), concentrated in vacuo, and resulting crude oil was purified using SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes) to give 1.5 g (65%) the title compound as a light yellow oil. 1H-NMR (CDCl3; 400 MHz) δ 8.18 (br s, 1H), 7.98–8.00 (m, 1H), 7.82–7.85 (m, 1H), 7.42–7.46 (m, 1H). 19F-NMR (CDCl3; 400 MHz) δ −72.06 (s). to warm up slowly to rt overnight the layers were separated the aqueous layer was extracted with another portion of EtOAc The combined organic fractions were dried (MgSO4) concentrated in vacuo resulting crude oil was purified SiO2 flash chromatography (elution: 5–20% EtOAc in hexanes)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Under argon and with stirring, 22.7 ml (22.7 mmol) of a 1 M solution of methylmagnesium bromide in diethyl ether were added dropwise at 0° C. to a solution of 5.22 g (20.6 mmol) of 1-(3-bromophenyl)-2,2,2-trifluoroethanone in 40 ml of anhydrous THF. After the addition had ended, the reaction mixture was stirred at 0° C. for another 30 min. Then—still at 0° C.—excess Grignard reagent was hydrolyzed by careful addition of water. The mixture was then adjusted to a pH of about 5 by addition of 2 M hydrochloric acid. The phases were separated and the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether. The combined organic phases were dried over magnesium sulphate, filtered and evaporated to dryness on a rotary evaporator. This gave 5.32 g (95% of theory) of the title compound. After the addition the reaction mixture was stirred at 0° C. for another 30 min The phases were separated the aqueous phase was extracted twice with in each case about 20 ml of diethyl ether The combined organic phases were dried over magnesium sulphate filtered evaporated to dryness on a rotary evaporator