4-fluoro-2-(trifluoromethyl)phenol

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9 g (500 mmol) of 4-fluoro-2-(trifluoromethyl)-phenol is dissolved in 100 ml of dichloroethane, the solution is stirred at 50° C. and a solution of 9.6 g (60 mmol) of bromine in 30 ml of dichloroethane is instilled in the course of 2 hours. When the instillation is completed, it is stirred for 1 more hour at 50° C. and then concentrated by evaporation in a vacuum. The oily residue is dissolved in 100 ml of dichloroethane and shaken out three times with 20 ml of water each. The organic phase is dried on magnesium sulfate, filtered, concentrated by evaporation and the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane. 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid. is instilled in the course of 2 hours it is stirred for 1 more hour at 50° C. concentrated by evaporation in a vacuum The oily residue is dissolved in 100 ml of dichloroethane shaken out three times with 20 ml of water each The organic phase is dried on magnesium sulfate filtered concentrated by evaporation the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9 g (500 mmol) of 4-fluoro-2-(trifluoromethyl)-phenol is dissolved in 100 ml of dichloroethane, the solution is stirred at 50° C. and a solution of 9.6 g (60 mmol) of bromine in 30 ml of dichloroethane is instilled in the course of 2 hours. When the instillation is completed, it is stirred for 1 more hour at 50° C. and then concentrated by evaporation in a vacuum. The oily residue is dissolved in 100 ml of dichloroethane and shaken out three times with 20 ml of water each. The organic phase is dried on magnesium sulfate, filtered, concentrated by evaporation and the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane. 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid. is instilled in the course of 2 hours it is stirred for 1 more hour at 50° C. concentrated by evaporation in a vacuum The oily residue is dissolved in 100 ml of dichloroethane shaken out three times with 20 ml of water each The organic phase is dried on magnesium sulfate filtered concentrated by evaporation the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid

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

実験手順: A mixture of 4-fluoro-2-(trifluoromethyl)phenol (1.05 g, 5.83 mmol), 2-bromoethanol (0.62 mL, 8.7 mmol) and triphenylphosphine (2.29 g, 8.73 mmol) in tetrahydrofuran (20 mL) was stirred for 5 minutes. Diisopropyl azodicarboxylate (94%, 1.84 mL, 8.71 mmol) was then added drop-wise over 20 minutes, and the reaction was stirred at room temperature for 16 hours. Water (50 mL) was added, and the mixture was extracted with dichloromethane (2×75 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 10% ethyl acetate in heptane) afforded the title compound as a white solid. Yield: 600 mg, 2.09 mmol, 36%. GCMS m/z 286. 1H NMR (400 MHz, CDCl3) δ 3.66 (dd, J=6.6, 6.4 Hz, 2H), 4.35 (dd, J=6.5, 6.4 Hz, 2H), 6.97 (br dd, J=9.0, 4.1 Hz, 1H), 7.18-7.24 (m, 1H), 7.32 (br dd, J=8.3, 3.2 Hz, 1H). the reaction was stirred at room temperature for 16 hours the mixture was extracted with dichloromethane (2×75 mL) The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL) dried over magnesium sulfate concentrated in vacuo Purification via silica gel chromatography (Gradient: 0% to 10% ethyl acetate in heptane)

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

実験手順: To a mixture of tert-butyl[(2S)-1-hydroxypropan-2-yl]carbamate (1.07 g, 6.11 mmol), 4-fluoro-2-(trifluoromethyl)phenol (1.10 g, 5.55 mmol) and triphenylphosphine-resin (2.80 g, 8.40 mmol) in tetrahydrofuran (50 mL) was added drop-wise diisopropyl azodicarboxylate (DIAD, 1.37 g, 6.66 mmol). The reaction was allowed to stir at room temperature for 3 days, then filtered and rinsed with ethyl acetate. The combined filtrate was washed with 0.5 N aqueous sodium hydroxide and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Purification via silica gel chromatography (50% ethyl acetate in heptane) afforded the title compound as a clear yellow oil. Sample contained some residual diisopropyl azodicarboxylate and carried forward without further purification. Yield: 2.52 g, 134%. LCMS m/z 282.0 {[M-(2-methyl-prop-1-ene)]+1}. 1H NMR (400 MHz, CDCl3) δ 1.31 (d, J=6.8 Hz, 3H), 1.45 (s, 9H), 3.98-4.03 (m, 2H), 4.04-4.13 (m, 1H), 6.95 (dd, J=9.2, 4.2 Hz, 1H), 7.16-7.22 (m, 1H), 7.30 (dd, J=8.3, 3.0 Hz, 1H). filtered rinsed with ethyl acetate The combined filtrate was washed with 0.5 N aqueous sodium hydroxide and saturated aqueous sodium chloride solution dried over magnesium sulfate filtered concentrated in vacuo Purification via silica gel chromatography (50% ethyl acetate in heptane)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9 g (500 mmol) of 4-fluoro-2-(trifluoromethyl)-phenol is dissolved in 100 ml of dichloroethane, the solution is stirred at 50° C. and a solution of 9.6 g (60 mmol) of bromine in 30 ml of dichloroethane is instilled in the course of 2 hours. When the instillation is completed, it is stirred for 1 more hour at 50° C. and then concentrated by evaporation in a vacuum. The oily residue is dissolved in 100 ml of dichloroethane and shaken out three times with 20 ml of water each. The organic phase is dried on magnesium sulfate, filtered, concentrated by evaporation and the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane. 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid. is instilled in the course of 2 hours it is stirred for 1 more hour at 50° C. concentrated by evaporation in a vacuum The oily residue is dissolved in 100 ml of dichloroethane shaken out three times with 20 ml of water each The organic phase is dried on magnesium sulfate filtered concentrated by evaporation the residue is chromatographed on silica gel 60 (Merck) ethyl acetate/hexane 8.07 g (31.15 mmol)=62.3% of the theoretical yield is obtained as a partially crystalline solid