2-ethyl-4,4,4-trifluorobutanoic acid

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of LAH (2.74 g, 72.3 mmol) in Et2O (230 mL) was stirred under nitrogen at 0° C. 2-Ethyl-4,4,4-trifluorobutyric acid (12.3 g, 72.3 mmol) in Et2O (20 mL) was added dropwise, and the solution stirred for 15 min at 0° C. and then 2 h at 25° C. After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring. Solid Na2SO4 was added to dry the solvent, and the resulting mixture was stirred for 1 h. The resulting slurry was filtered, and the filter cake washed with excess Et2O. After concentration, the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent: 20:80 to 30:70 Et2O:PE to obtain 2-ethyl-4,4,4-trifluorobutanol as an oil (6.18 g, 55% yield for two steps). 2 h at 25° C After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring Solid Na2SO4 was added to dry the solvent the resulting mixture was stirred for 1 h The resulting slurry was filtered the filter cake washed with excess Et2O After concentration the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of LAH (2.74 g, 72.3 mmol) in Et2O (230 mL) was stirred under nitrogen at 0° C. 2-Ethyl-4,4,4-trifluorobutyric acid (12.3 g, 72.3 mmol) in Et2O (20 mL) was added dropwise, and the solution stirred for 15 min at 0° C. and then 2 h at 25° C. After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring. Solid Na2SO4 was added to dry the solvent, and the resulting mixture was stirred for 1 h. The resulting slurry was filtered, and the filter cake washed with excess Et2O. After concentration, the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent: 20:80 to 30:70 Et2O:PE to obtain 2-ethyl-4,4,4-trifluorobutanol as an oil (6.18 g, 55% yield for two steps). 2 h at 25° C After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring Solid Na2SO4 was added to dry the solvent the resulting mixture was stirred for 1 h The resulting slurry was filtered the filter cake washed with excess Et2O After concentration the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of LAH (2.74 g, 72.3 mmol) in Et2O (230 mL) was stirred under nitrogen at 0° C. 2-Ethyl-4,4,4-trifluorobutyric acid (12.3 g, 72.3 mmol) in Et2O (20 mL) was added dropwise, and the solution stirred for 15 min at 0° C. and then 2 h at 25° C. After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring. Solid Na2SO4 was added to dry the solvent, and the resulting mixture was stirred for 1 h. The resulting slurry was filtered, and the filter cake washed with excess Et2O. After concentration, the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent: 20:80 to 30:70 Et2O:PE to obtain 2-ethyl-4,4,4-trifluorobutanol as an oil (6.18 g, 55% yield for two steps). 2 h at 25° C After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring Solid Na2SO4 was added to dry the solvent the resulting mixture was stirred for 1 h The resulting slurry was filtered the filter cake washed with excess Et2O After concentration the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylamine (17.1 g, 169 mmol) in THF (180 mL) was stirred under nitrogen at 0° C. n-Butyl lithium (n-BuLi—67.6 mL, 2.5 M in hexane) was added dropwise over 15 min and the resulting solution stirred for 0.5 h at 0° C. After this time period, the reaction was cooled to −78° C., and 4,4,4-trifluorobutyric acid (10.0 g, 70.4 mmol) in THF (20 mL) was added dropwise over 0.5 h. The resulting solution was stirred for an additional 0.5 h at −78° C. After this time period, ethyl iodide (6.19 mL, 77.4 mmol) was added dropwise over 15 min. The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h. After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL). After concentration, the residue was acidified to pH 1 with 2 N aq. HCl and then extracted with Et2O (400 mL). The organic layer was then dried using MgSO4. After concentration, the resulting residue was used directly in the next reaction without further purification. was added dropwise over 15 min After this time period, the reaction was cooled to −78° C. The resulting solution was stirred for an additional 0.5 h at −78° C The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL) After concentration extracted with Et2O (400 mL) The organic layer was then dried After concentration the resulting residue was used directly in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylamine (17.1 g, 169 mmol) in THF (180 mL) was stirred under nitrogen at 0° C. n-Butyl lithium (n-BuLi—67.6 mL, 2.5 M in hexane) was added dropwise over 15 min and the resulting solution stirred for 0.5 h at 0° C. After this time period, the reaction was cooled to −78° C., and 4,4,4-trifluorobutyric acid (10.0 g, 70.4 mmol) in THF (20 mL) was added dropwise over 0.5 h. The resulting solution was stirred for an additional 0.5 h at −78° C. After this time period, ethyl iodide (6.19 mL, 77.4 mmol) was added dropwise over 15 min. The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h. After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL). After concentration, the residue was acidified to pH 1 with 2 N aq. HCl and then extracted with Et2O (400 mL). The organic layer was then dried using MgSO4. After concentration, the resulting residue was used directly in the next reaction without further purification. was added dropwise over 15 min After this time period, the reaction was cooled to −78° C. The resulting solution was stirred for an additional 0.5 h at −78° C The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL) After concentration extracted with Et2O (400 mL) The organic layer was then dried After concentration the resulting residue was used directly in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of LAH (2.74 g, 72.3 mmol) in Et2O (230 mL) was stirred under nitrogen at 0° C. 2-Ethyl-4,4,4-trifluorobutyric acid (12.3 g, 72.3 mmol) in Et2O (20 mL) was added dropwise, and the solution stirred for 15 min at 0° C. and then 2 h at 25° C. After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring. Solid Na2SO4 was added to dry the solvent, and the resulting mixture was stirred for 1 h. The resulting slurry was filtered, and the filter cake washed with excess Et2O. After concentration, the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent: 20:80 to 30:70 Et2O:PE to obtain 2-ethyl-4,4,4-trifluorobutanol as an oil (6.18 g, 55% yield for two steps). 2 h at 25° C After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring Solid Na2SO4 was added to dry the solvent the resulting mixture was stirred for 1 h The resulting slurry was filtered the filter cake washed with excess Et2O After concentration the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylamine (17.1 g, 169 mmol) in THF (180 mL) was stirred under nitrogen at 0° C. n-Butyl lithium (n-BuLi—67.6 mL, 2.5 M in hexane) was added dropwise over 15 min and the resulting solution stirred for 0.5 h at 0° C. After this time period, the reaction was cooled to −78° C., and 4,4,4-trifluorobutyric acid (10.0 g, 70.4 mmol) in THF (20 mL) was added dropwise over 0.5 h. The resulting solution was stirred for an additional 0.5 h at −78° C. After this time period, ethyl iodide (6.19 mL, 77.4 mmol) was added dropwise over 15 min. The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h. After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL). After concentration, the residue was acidified to pH 1 with 2 N aq. HCl and then extracted with Et2O (400 mL). The organic layer was then dried using MgSO4. After concentration, the resulting residue was used directly in the next reaction without further purification. was added dropwise over 15 min After this time period, the reaction was cooled to −78° C. The resulting solution was stirred for an additional 0.5 h at −78° C The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL) After concentration extracted with Et2O (400 mL) The organic layer was then dried After concentration the resulting residue was used directly in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of LAH (2.74 g, 72.3 mmol) in Et2O (230 mL) was stirred under nitrogen at 0° C. 2-Ethyl-4,4,4-trifluorobutyric acid (12.3 g, 72.3 mmol) in Et2O (20 mL) was added dropwise, and the solution stirred for 15 min at 0° C. and then 2 h at 25° C. After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring. Solid Na2SO4 was added to dry the solvent, and the resulting mixture was stirred for 1 h. The resulting slurry was filtered, and the filter cake washed with excess Et2O. After concentration, the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent: 20:80 to 30:70 Et2O:PE to obtain 2-ethyl-4,4,4-trifluorobutanol as an oil (6.18 g, 55% yield for two steps). 2 h at 25° C After this time period, the solution was quenched with the dropwise addition of H2O (2.74 mL), 15% NaOH (2.74 mL), and H2O (8.22 mL) with efficient stirring Solid Na2SO4 was added to dry the solvent the resulting mixture was stirred for 1 h The resulting slurry was filtered the filter cake washed with excess Et2O After concentration the crude product was purified by the Biotage Flash™ 40 chromatography instrument, eluent

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of diisopropylamine (17.1 g, 169 mmol) in THF (180 mL) was stirred under nitrogen at 0° C. n-Butyl lithium (n-BuLi-67.6 mL, 2.5 M in hexane) was added dropwise over 15 min and the resulting solution stirred for 0.5 h at 0° C. After this time period, the reaction was cooled to −78° C., and 4,4,4-trifluorobutyric acid (10.0 g, 70.4 mmol) in THF (20 mL) was added dropwise over 0.5 h. The resulting solution was stirred for an additional 0.5 h at −78° C. After this time period, ethyl iodide (6.19 mL, 77.4 mmol) was added dropwise over 15 min. The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h. After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL). After concentration, the residue was acidified to pH 1 with 2 N aq. HCl and then extracted with Et2O (400 mL). The organic layer was then dried using MgSO4. After concentration, the resulting residue was used directly in the next reaction without further purification. was added dropwise over 15 min After this time period, the reaction was cooled to −78° C. The resulting solution was stirred for an additional 0.5 h at −78° C The resulting solution was stirred for 15 min. at −78° C. then warmed to 25° C. for 24 h After this time period, the reaction mixture was quenched by slow addition of H2O (˜20 mL) After concentration extracted with Et2O (400 mL) The organic layer was then dried After concentration the resulting residue was used directly in the next reaction without further purification