2-bromo-3,3,3-trifluoroprop-1-ene

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:0.00; 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:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a solution of 25.0 g of 3,5-dichlorophenyl boric acid in 200 ml of tetrahydrofuran and 100 ml of water, 27.5 g of 2-bromo-3,3,3-trifluoropropene, 38.0 g of potassium carbonate and 1.84 g of dichlorobis(triphenylphosphine) palladium (II) were added, and stirred under reflux with heat for 3 hours. After the completion of the reaction and cooling to room temperature, 500 ml of ice water was added, and extracted with ethyl acetate (500 ml×1). The organic phase was washed with water, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that was eluated with hexane, and 25.7 g of the aimed product was obtained as colorless oily substance. under reflux with heat for 3 hours After the completion of the reaction extracted with ethyl acetate (500 ml×1) The organic phase was washed with water dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was purified with silica gel column chromatography that

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of LDA (2 M in THF, 3.2 mL, 6.4 mmol) in anhydrous THF (10 mL) was added dropwise 2-bromo-3,3,3-trifluoroprop-1-ene (0.55 g, 3.1 mmol) at −78° C. The resulting mixture was stirred at that temperature for 15 minutes, followed by the addition of ZnCl2 (1 M in ethyl ether, 6.5 mL, 6.5 mmol) and TMEDA (1 mL, 6.5 mmol). The mixture was stirred at −78° C. for further 30 minutes and then 30 minutes at room temperature. 5-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.99 g, 3.0 mmol) and Pd(PPh3)4 (0.21 g, 0.18 mmol) were added. The reaction mixture was heated at 80° C. for 6 hours under N2 atmosphere. Upon completion, the reaction mixture was quenched with water (100 mL) and then diluted with ethyl acetate (300 mL). The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜20% EtOAc in petroleum ether) affording the title compound (299 mg). 1H NMR (300 MHz, DMSO-d6): δ 8.28 (s, 1H), 8.24 (s, 1H), 7.87 (d, 1H), 7.68 (dd, 1H), 5.91 (dd, 1H), 3.90-3.86 (m, 1H), 3.79-3.72 (m, 1H), 2.41-2.36 (m, 1H), 2.05-1.96 (m, 2H), 1.76-1.72 (m, 1H), 1.60-1.56 (m, 2H); LCMS: 295 (M+H)+. The mixture was stirred at −78° C. for further 30 minutes 30 minutes at room temperature Upon completion, the reaction mixture was quenched with water (100 mL) diluted with ethyl acetate (300 mL) The organic layer was separated dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography on silica gel (0˜20% EtOAc in petroleum ether)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of LDA (2 M in THF, 3.2 mL, 6.4 mmol) in anhydrous THF (10 mL) was added dropwise 2-bromo-3,3,3-trifluoroprop-1-ene (0.55 g, 3.1 mmol) at −78° C. The resulting mixture was stirred at that temperature for 15 minutes, followed by the addition of ZnCl2 (1 M in ethyl ether, 6.5 mL, 6.5 mmol) and TMEDA (1 mL, 6.5 mmol). The mixture was stirred at −78° C. for further 30 minutes and then 30 minutes at room temperature. 5-Iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (0.99 g, 3.0 mmol) and Pd(PPh3)4 (0.21 g, 0.18 mmol) were added. The reaction mixture was heated at 80° C. for 6 hours under N2 atmosphere. Upon completion, the reaction mixture was quenched with water (100 mL) and then diluted with ethyl acetate (300 mL). The organic layer was separated, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜20% EtOAc in petroleum ether) affording the title compound (299 mg). 1H NMR (300 MHz, DMSO-d6): δ 8.28 (s, 1H), 8.24 (s, 1H), 7.87 (d, 1H), 7.68 (dd, 1H), 5.91 (dd, 1H), 3.90-3.86 (m, 1H), 3.79-3.72 (m, 1H), 2.41-2.36 (m, 1H), 2.05-1.96 (m, 2H), 1.76-1.72 (m, 1H), 1.60-1.56 (m, 2H); LCMS: 295 (M+H)+. The mixture was stirred at −78° C. for further 30 minutes 30 minutes at room temperature Upon completion, the reaction mixture was quenched with water (100 mL) diluted with ethyl acetate (300 mL) The organic layer was separated dried over Na2SO4 concentrated in vacuo The residue was purified by column chromatography on silica gel (0˜20% EtOAc in 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-bromo-3,3,3-trifluoro-1-propene (1 g, 5.716 mmol) in diethyl ether (2 ml) cooled with ice-bath under N2 atmosphere a solution of ethyl diazoacetate (1.06 ml, 8.574 mmol) in diethyl ether (3 ml) was added drop wise. The mixture was warmed to RT and then refluxed for 3 hours. The volatiles were removed under vacuum. Vacuum distillation provided the title compound. was added drop wise refluxed for 3 hours The volatiles were removed under vacuum Vacuum distillation

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3,4,5-trichlorophenylboronic acid (4.5 g, 20 mmol), 2-bromo-3,3,3-trifluoro-prop-1-ene (4.9 g, 28 mmol), Cs2CO3 (20 mL, 2 M, 40 mmol) and Pd(PPh3)2Cl2 (421 mg) in THF (30 mL) was heated at 70° C. in a sealed tube for 4 h. The mixture was cooled to rt and partitioned between ether and H2O. The aqueous layer was extracted with EA and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography over silica gel eluted with hexanes to give 1,2,3-trichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (4.3 g; yield 80%). 1H NMR (500 MHz, CDCl3): δ 7.40 (s, 2H), 5.99 (s, 1H), 5.76 (s, 1H) ppm. The mixture was cooled to rt partitioned between ether and H2O The aqueous layer was extracted with EA the combined organic layers were dried over Na2SO4 The solvent was removed under reduced pressure the crude product was purified by column chromatography over silica gel eluted with hexanes

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 3,5-dichlorophenylboronic acid (3.8 g, 20.0 mmol), 2-bromo-3,3,3-trifluoro-prop-1-ene (4.9 g, 28 mmol), Cs2CO3 (20 mL, 2 M, 40 mmol) and Pd(PPh3)2Cl2 (421 mg) in THF (30 mL) was heated at 70° C. in a sealed tube for 4 h. The mixture was cooled to rt and partitioned between ether and H2O. The aqueous layer was extracted with EA and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography over silica gel eluted with hexanes to give 1,3-dichloro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (3.85 g; yield 80%). 1H NMR (500 MHz, CDCl3): δ 7.41 (s, 1H), 7.35 (s, 2H), 6.06 (s, 1 H), 5.83 (s, 1 H) ppm. The mixture was cooled to rt partitioned between ether and H2O The aqueous layer was extracted with EA the combined organic layers were dried over Na2SO4 The solvent was removed under reduced pressure the crude product was purified by column chromatography over silica gel eluted with hexanes