1-(2-bromophenyl)-2,2,2-trifluoroethanol

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:; See reaction.notes.procedure_details.

実験手順: Thiophosgene (24.0 g, 210.0 mmol) was added portion-wise to a vigorously stirred suspension of imidazole (57.0 g, 840.0 mmol) in 1,2-dichloroethane (500 ml) under an atmosphere of nitrogen. After the addition, the reaction mixture was stirred at room temperature for 30 minutes. 1-(2-Bromophenyl)-2,2,2-trifluoro-ethanol (Preparation 55, 46 g, crude, about 140 mmol) in 1,2-dichloroethane (100 m) was added at room temperature. After the addition, the mixture was heated at reflux for 10 minutes. The reaction mixture was cooled then the solvent was evaporated in vacuo. The crude product was purified by column chromatography on silica gel eluting with petroleum ether, then petroleum ether:ethyl acetate (10:1) to afford the title compound as a yellow oil (41.5 g, 81%). After the addition After the addition the mixture was heated at reflux for 10 minutes The reaction mixture was cooled the solvent was evaporated in vacuo The crude product was purified by column chromatography on silica gel eluting with petroleum ether

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

実験手順: To a solution of 2-bromobenzaldehyde (27.0 g, 146.5 mmol) and trimethylsilyl-trifluoromethane (25.0 g, 175.8 mmol) in tetrahydrofuran (300 ml) was added drop-wise tetrabutylammonium fluoride (1 M in tetrahydrofuran, 5 ml, 5 mmol) at 0° C. After the addition, the mixture was stirred at room temperature for 2 hours. Further tetrabutylammonium fluoride hydrate (49.0 g, 175.8 mmol) was added and the mixture was stirred for 30 minutes. The solvent was evaporated in vacuo. The residue was dissolved in dichloromethane (200 ml) and washed with hydrochloric acid (2N aqueous solution) (4×100 ml). The organic layer was separated, washed with Na2CO3 (10% aqueous solution) (50 ml), dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo to afford the crude title compound as a yellow oil (45.0 g, ˜100%). After the addition the mixture was stirred for 30 minutes The solvent was evaporated in vacuo The residue was dissolved in dichloromethane (200 ml) washed with hydrochloric acid (2N aqueous solution) (4×100 ml) The organic layer was separated washed with Na2CO3 (10% aqueous solution) (50 ml) dried over anhydrous MgSO4 (s) filtered evaporated in vacuo

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:; See reaction.notes.procedure_details.

実験手順: The title compound was prepared by an adaptation of the method described in Robins, M. J. et al. (J. Am. Chem. Soc. 1983, 105, 4059-4065). 1-(2-Bromo-phenyl)-2,2,2-trifluoro-ethanol (615 mg, 2.41 mmol, as prepared in the previous step) was placed in an 8 mL vial equipped with a magnetic stir bar. DCM (4 mL) and TEA (1.2 eq., 0.403 mL, 2.89 mmol) were added via syringe. Phenyl chlorothionoformate (1.1 eq., 0.367 mL, 2.65 mmol) was added dropwise via syringe to the water-cooled solution. After completion of the addition, the reaction was stirred at RT for 16 h, poured into water, and extracted three times with DCM (10 mL). The combined organic extracts were dried over anhydrous MgSO4 filtered, and the solvent was removed under reduced pressure. The crude product was purified by column chromatography using a 12-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 1:4, v/v over 30 min, yielding 695 mg (74%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 7.58-7.68 (m, 2H), 7.36-7.48 (m, 3H), 7.27-7.36 (m, 2H), 7.04-7.15 (m, 3H). The title compound was prepared by an adaptation of the method vial equipped with a magnetic stir bar cooled solution After completion of the addition extracted three times with DCM (10 mL) The combined organic extracts were dried over anhydrous MgSO4 filtered the solvent was removed under reduced pressure The crude product was purified by column chromatography eluting with EtOAc/hexanes, 0:1 to 1:4, v/v over 30 min

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

実験手順: The title compound was prepared by an adaptation of the method described in Xue, Y. et al. (Bioorg. Med. Chem. 2007, 15, 2156-2166). Tetrabutylammonium fluoride hydrate (0.05 eq., 131 mg, 0.050 mmol) was placed in a 40 mL vial equipped with a magnetic stir bar, and the vial was evacuated and backflushed with Ar. Dry THF (25 mL) was added via syringe, and 2-bromobenzaldehyde (1.16 mL, 10.0 mmol) and trimethylsilyltrifluoromethane (1.3 eq., 1.90 mL, 13.0 mmol) were sequentially added via syringe. The reaction was stirred at RT for 16 h, and additional CF3 TMS (1 mL) was added. After stirring for 2 h, the reaction was poured into 3 M aq HCl (30 mL) and stirred at RT for 2 h. The reaction mixture was extracted three times with DCM (30 mL), and the combined organic extracts were dried over anhydrous MgSO4, filtered, and the solvent removed under reduced pressure, yielding 1.83 g (72%) of the title compound. 1H-NMR (400 MHz, CDCl3) δ: 7.69 (d, J=7.8 Hz, 1H), 7.60 (dd, J=8.1, 1.3 Hz, 1H), 7.40 (td, J=7.6, 1.1 Hz, 1H), 7.27 (td, J=7.7, 1.8 Hz, 1H), 5.56-5.68 (m, 1H), 2.77 (d, J=4.8 Hz, 1H). The title compound was prepared by an adaptation of the method vial equipped with a magnetic stir bar the vial was evacuated Dry THF (25 mL) was added via syringe After stirring for 2 h stirred at RT for 2 h The reaction mixture was extracted three times with DCM (30 mL) the combined organic extracts were dried over anhydrous MgSO4 filtered the solvent removed under reduced pressure

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

実験手順: Thiophosgene (24.0 g, 210.0 mmol) was added portion-wise to a vigorously stirred suspension of imidazole (57.0 g, 840.0 mmol) in 1,2-dichloroethane (500 ml) under an atmosphere of nitrogen. After the addition, the reaction mixture was stirred at room temperature for 30 minutes. 1-(2-Bromophenyl)-2,2,2-trifluoro-ethanol (Preparation 55, 46 g, crude, about 140 mmol) in 1,2-dichloroethane (100 m) was added at room temperature. After the addition, the mixture was heated at reflux for 10 minutes. The reaction mixture was cooled then the solvent was evaporated in vacuo. The crude product was purified by column chromatography on silica gel eluting with petroleum ether, then petroleum ether:ethyl acetate (10:1) to afford the title compound as a yellow oil (41.5 g, 81%). After the addition After the addition the mixture was heated at reflux for 10 minutes The reaction mixture was cooled the solvent was evaporated in vacuo The crude product was purified by column chromatography on silica gel eluting with petroleum ether

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

実験手順: To a solution of 2-bromobenzaldehyde (27.0 g, 146.5 mmol) and trimethylsilyl-trifluoromethane (25.0 g, 175.8 mmol) in tetrahydrofuran (300 ml) was added drop-wise tetrabutylammonium fluoride (1 M in tetrahydrofuran, 5 ml, 5 mmol) at 0° C. After the addition, the mixture was stirred at room temperature for 2 hours. Further tetrabutylammonium fluoride hydrate (49.0 g, 175.8 mmol) was added and the mixture was stirred for 30 minutes. The solvent was evaporated in vacuo. The residue was dissolved in dichloromethane (200 ml) and washed with hydrochloric acid (2N aqueous solution) (4×100 ml). The organic layer was separated, washed with Na2CO3 (10% aqueous solution) (50 ml), dried over anhydrous MgSO4 (s), filtered and evaporated in vacuo to afford the crude title compound as a yellow oil (45.0 g, ˜100%). After the addition the mixture was stirred for 30 minutes The solvent was evaporated in vacuo The residue was dissolved in dichloromethane (200 ml) washed with hydrochloric acid (2N aqueous solution) (4×100 ml) The organic layer was separated washed with Na2CO3 (10% aqueous solution) (50 ml) dried over anhydrous MgSO4 (s) filtered evaporated in vacuo