2-Methyl-4,4,4-trifluorobutyryl chloride

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (3.22 g) and tetrahydrofuran (35 ml) at -70° C., under nitrogen was added 1.625M n-butyllithium (12.31 mL) and the mixture was stirred for 15 min. 2-Methyl-4,4,4-trifluorobutyryl chloride (3.5 g) was added to the reaction mixture which was stirred for 15 min at -70° C. and then at 0° C. for 1 hour. The reaction was quenched with ammonium chloride and extracted with ethyl acetate. The organic phase was washed (saturated NaHCO3, brine) and dried (MgSO4). Evaporation and flash chromatography, eluting with 5:95 then 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products. Recrystallization from hexane at 20° C. gave (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (2.376 g, 42%) as colorless needles; mp 72.5°-73.5° C.; TLC, Rf =0.43, 1:9 ethyl acetate:petroleum ether; MS(CI): 316 (M+H). was stirred for 15 min at -70° C. at 0° C. for 1 hour The reaction was quenched with ammonium chloride extracted with ethyl acetate The organic phase was washed (saturated NaHCO3, brine) dried (MgSO4) Evaporation and flash chromatography eluting with 5:95 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products Recrystallization from hexane at 20° C.

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 0° C., 16.44 g (123.3 mmol) of aluminum chloride were added a little at a time to 12.6 ml (118.6 mmol) of toluene and 20.9 g (119.7 mmol) of 4,4,4-trifluoro-2-methylbutanoyl chloride in 300 ml of 1,2-dichloroethane, and the mixture was stirred at 0° C. for one hour. The reaction mixture was then slowly warmed to room temperature and stirred at this temperature for three hours. The reaction mixture was then slowly added to 300 ml of ice-cooled 18.5% strength hydrochloric acid, and the organic phase was then removed. The aqueous phase was extracted three more times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gave 19.96 g (18.7 mmol, 73% of theory) of the title compound. The reaction mixture was then slowly warmed to room temperature stirred at this temperature for three hours the organic phase was then removed The aqueous phase was extracted three more times with dichloromethane The combined organic phases were dried over sodium sulfate filtered the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 0° C., 16.44 g (123.3 mmol) of aluminum chloride were added a little at a time to 12.6 ml (118.6 mmol) of toluene and 20.9 g (119.7 mmol) of 4,4,4-trifluoro-2-methylbutanoyl chloride in 300 ml of 1,2-dichloroethane, and the mixture was stirred at 0° C. for one hour. The reaction mixture was then slowly warmed to room temperature and stirred at this temperature for three hours. The reaction mixture was then slowly added to 300 ml of ice-cooled 18.5% strength hydrochloric acid, and the organic phase was then removed. The aqueous phase was extracted three more times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gave 19.96 g (18.7 mmol, 73% of theory) of the title compound. The reaction mixture was then slowly warmed to room temperature stirred at this temperature for three hours the organic phase was then removed The aqueous phase was extracted three more times with dichloromethane The combined organic phases were dried over sodium sulfate filtered the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (3.22 g) and tetrahydrofuran (35 ml) at -70° C., under nitrogen was added 1.625M n-butyllithium (12.31 mL) and the mixture was stirred for 15 min. 2-Methyl-4,4,4-trifluorobutyryl chloride (3.5 g) was added to the reaction mixture which was stirred for 15 min at -70° C. and then at 0° C. for 1 hour. The reaction was quenched with ammonium chloride and extracted with ethyl acetate. The organic phase was washed (saturated NaHCO3, brine) and dried (MgSO4). Evaporation and flash chromatography, eluting with 5:95 then 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products. Recrystallization from hexane at 20° C. gave (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (2.376 g, 42%) as colorless needles; mp 72.5°-73.5° C.; TLC, Rf =0.43, 1:9 ethyl acetate:petroleum ether; MS(CI): 316 (M+H). was stirred for 15 min at -70° C. at 0° C. for 1 hour The reaction was quenched with ammonium chloride extracted with ethyl acetate The organic phase was washed (saturated NaHCO3, brine) dried (MgSO4) Evaporation and flash chromatography eluting with 5:95 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products Recrystallization from hexane at 20° C.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (3.22 g) and tetrahydrofuran (35 ml) at -70° C., under nitrogen was added 1.625M n-butyllithium (12.31 mL) and the mixture was stirred for 15 min. 2-Methyl-4,4,4-trifluorobutyryl chloride (3.5 g) was added to the reaction mixture which was stirred for 15 min at -70° C. and then at 0° C. for 1 hour. The reaction was quenched with ammonium chloride and extracted with ethyl acetate. The organic phase was washed (saturated NaHCO3, brine) and dried (MgSO4). Evaporation and flash chromatography, eluting with 5:95 then 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products. Recrystallization from hexane at 20° C. gave (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (2.376 g, 42%) as colorless needles; mp 72.5°-73.5° C.; TLC, Rf =0.43, 1:9 ethyl acetate:petroleum ether; MS(CI): 316 (M+H). was stirred for 15 min at -70° C. at 0° C. for 1 hour The reaction was quenched with ammonium chloride extracted with ethyl acetate The organic phase was washed (saturated NaHCO3, brine) dried (MgSO4) Evaporation and flash chromatography eluting with 5:95 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products Recrystallization from hexane at 20° C.

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 2-methyl-4,4,4-trifluorobutyric acid (172 g) in methylene chloride (150 mL) and N,N-dimethylformamide (3.5 mL) at 0° C., under nitrogen was added (dropwise) oxalyl chloride (125 mL). The mixture was allowed to warm to ambient temperature and stirred for 16 hours. After distillation of the solvent, distillation using a concentric tube distillation column (40 cm×15 mm) afforded 2-methyl-4,4,4-trifluorobutyryl chloride (about 99% purity, 79.87 g, 42%); bp 115.0°-116.0° C. (at atmospheric pressure, measured at room temperature as 763.27 mm Hg); GLC: tR =5.04 min; MS(CI): 139 (M+H-HCl). After distillation of the solvent, distillation distillation column (40 cm×15 mm)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 2-methyl-4,4,4-trifluorobutyric acid (172 g) in methylene chloride (150 mL) and N,N-dimethylformamide (3.5 mL) at 0° C., under nitrogen was added (dropwise) oxalyl chloride (125 mL). The mixture was allowed to warm to ambient temperature and stirred for 16 hours. After distillation of the solvent, distillation using a concentric tube distillation column (40 cm×15 mm) afforded 2-methyl-4,4,4-trifluorobutyryl chloride (about 99% purity, 79.87 g, 42%); bp 115.0°-116.0° C. (at atmospheric pressure, measured at room temperature as 763.27 mm Hg); GLC: tR =5.04 min; MS(CI): 139 (M+H-HCl). After distillation of the solvent, distillation distillation column (40 cm×15 mm)

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: At 0° C., 16.44 g (123.3 mmol) of aluminum chloride were added a little at a time to 12.6 ml (118.6 mmol) of toluene and 20.9 g (119.7 mmol) of 4,4,4-trifluoro-2-methylbutanoyl chloride in 300 ml of 1,2-dichloroethane, and the mixture was stirred at 0° C. for one hour. The reaction mixture was then slowly warmed to room temperature and stirred at this temperature for three hours. The reaction mixture was then slowly added to 300 ml of ice-cooled 18.5% strength hydrochloric acid, and the organic phase was then removed. The aqueous phase was extracted three more times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1). This gave 19.96 g (18.7 mmol, 73% of theory) of the title compound. The reaction mixture was then slowly warmed to room temperature stirred at this temperature for three hours the organic phase was then removed The aqueous phase was extracted three more times with dichloromethane The combined organic phases were dried over sodium sulfate filtered the solvent was removed under reduced pressure The crude product was purified chromatographically on silica gel (mobile phase cyclohexane/ethyl acetate 4:1)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone (3.22 g) and tetrahydrofuran (35 ml) at -70° C., under nitrogen was added 1.625M n-butyllithium (12.31 mL) and the mixture was stirred for 15 min. 2-Methyl-4,4,4-trifluorobutyryl chloride (3.5 g) was added to the reaction mixture which was stirred for 15 min at -70° C. and then at 0° C. for 1 hour. The reaction was quenched with ammonium chloride and extracted with ethyl acetate. The organic phase was washed (saturated NaHCO3, brine) and dried (MgSO4). Evaporation and flash chromatography, eluting with 5:95 then 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products. Recrystallization from hexane at 20° C. gave (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone (2.376 g, 42%) as colorless needles; mp 72.5°-73.5° C.; TLC, Rf =0.43, 1:9 ethyl acetate:petroleum ether; MS(CI): 316 (M+H). was stirred for 15 min at -70° C. at 0° C. for 1 hour The reaction was quenched with ammonium chloride extracted with ethyl acetate The organic phase was washed (saturated NaHCO3, brine) dried (MgSO4) Evaporation and flash chromatography eluting with 5:95 1:9 ethyl acetate:petroelum ether, afforded the two diastereomeric products Recrystallization from hexane at 20° C.