(2-bromo-4-fluorophenyl)methanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charged (2-bromo-4-fluorophenyl)methanol (954 mg, 4.65 mmol), 4-fluoro-1-vinylbenzene (1.14 g, 9.31 mmol), Pd(PPh3)2Cl2(49 mg, 0.07 mmol), Et3N (942 mg, 9.31 mmol) and DMF (5 mL) to a sealed tube, the mixture was then purged with nitrogen, heated to 150° C. for 3 h in microwave oven. The reaction mixture was filtered, the filtrate was then extracted with ethyl acetate, concentrated and purified by flash column chromatograph to give 569 mg of the title compound (50%). 1H NMR (400 MHz, CDCl3): δ 1.60 (1H, t, J=6.4 Hz), 4.78 (2H, d, J=6.4 Hz), 6.93-7.08 (4H, m), 7.31-7.35 (3H, m), 7.48-7.52 (2H, m). the mixture was then purged with nitrogen The reaction mixture was filtered the filtrate was then extracted with ethyl acetate concentrated purified by flash column chromatograph

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charged (2-bromo-4-fluorophenyl)methanol (954 mg, 4.65 mmol), 4-fluoro-1-vinylbenzene (1.14 g, 9.31 mmol), Pd(PPh3)2Cl2 (49 mg, 0.07 mmol), Et3N (942 mg, 9.31 mmol) and DMF (5 mL) to a sealed tube, the mixture was then purged with nitrogen, heated to 150° C. for 3 h in microwave oven. The reaction mixture was filtered, the filtrate was then extracted with ethyl acetate, concentrated and purified by flash column chromatograph to give 569 mg of the title compound (50%). 1H NMR (400 MHz, CDCl3): δ 1.60 (1H, t, J=6.4 Hz), 4.78 (2H, d, J=6.4 Hz), 6.93-7.08 (4H, m), 7.31-7.35 (3H, m), 7.48-7.52 (2H, m). the mixture was then purged with nitrogen The reaction mixture was filtered the filtrate was then extracted with ethyl acetate concentrated purified by flash column chromatograph

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: To a solution of 2-bromo-4-fluorobenzoic acid (20 g, 91 mmol) in anhydrous THF (300 ml) at −10° C. was added dropwise borane tetrahydrofuran complex (1.0M soln in THF) (136.5 ml, 136.5 mmol). After complete addition the reaction was allowed to stir at room temperature for 4 hours. The reaction was quenched by the dropwise addition of water (20 ml). To the mixture was added saturated K2CO3 (200 ml) and water (300 ml). The organic layer was separated and the aqueous extracted with Et2O (2×300 ml). The combined organics were washed with water (2×500 ml), saturated NaCl (200 ml), dried over Na2SO4, filtered and evaporated to give the title compound (18 g, 96%) as a white solid. After complete addition the reaction The reaction was quenched by the dropwise addition of water (20 ml) To the mixture was added saturated K2CO3 (200 ml) and water (300 ml) The organic layer was separated the aqueous extracted with Et2O (2×300 ml) The combined organics were washed with water (2×500 ml), saturated NaCl (200 ml) dried over Na2SO4 filtered evaporated

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a −78° C. cooled solution of oxalyl chloride (8.43 ml; 96.58 mmol) in anhydrous dichloromethane (300 ml) was added dropwise dimethyl sulfoxide (13.71 ml; 193.16 mmol). The mixture was stirred at −78° C. for 5 minutes then a solution of (2-bromo-4-fluorophenyl)methanol (Description 77, 18 g; 87.8 mmol) in anhydrous dichloromethane (150 ml) was added slowly. The resulting mixture was stirred at −78° C. for 15 minutes then triethylamine (36.71 ml; 263.4 mmol) was added and the mixture allowed to warm to room temperature over 1 hour. The mixture was washed with water (2×500 ml), saturated NaCl (200 ml), dried over Na2SO4, filtered through a 2 inch plug of silica gel and evaporated to give the title compound (16 g, 89%) as a white solid. The resulting mixture was stirred at −78° C. for 15 minutes to warm to room temperature over 1 hour The mixture was washed with water (2×500 ml), saturated NaCl (200 ml) dried over Na2SO4 filtered through a 2 inch plug of silica gel evaporated

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-4-fluorobenzoic acid (20 g; 91 mmol) in anhydrous THF (300 ml) at −10° C. was added dropwise borane tetrahydrofuran complex (1.0M soln in THF) (136.5 ml; 136.5 mmol). After complete addition the reaction was allowed to stir at room temperature for 4 hours. The reaction was quenched by the dropwise addition of water (20 ml). To the mixture was added saturated K2CO3 (200 ml) and water (300 ml). The organic layer was separated and the aqueous extracted with Et2O (2×300 ml). The combined organics were washed with water (2×500 ml), saturated NaCl (200 ml), dried over Na2SO4, filtered and evaporated to give the title compound (18 g, 96%) as a white solid. After complete addition the reaction The reaction was quenched by the dropwise addition of water (20 ml) To the mixture was added saturated K2CO3 (200 ml) and water (300 ml) The organic layer was separated the aqueous extracted with Et2O (2×300 ml) The combined organics were washed with water (2×500 ml), saturated NaCl (200 ml) dried over Na2SO4 filtered evaporated

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charged (2-bromo-4-fluorophenyl)methanol (954 mg, 4.65 mmol), 4-fluoro-1-vinylbenzene (1.14 g, 9.31 mmol), Pd(PPh3)2Cl2(49 mg, 0.07 mmol), Et3N (942 mg, 9.31 mmol) and DMF (5 mL) to a sealed tube, the mixture was then purged with nitrogen, heated to 150° C. for 3 h in microwave oven. The reaction mixture was filtered, the filtrate was then extracted with ethyl acetate, concentrated and purified by flash column chromatograph to give 569 mg of the title compound (50%). 1H NMR (400 MHz, CDCl3): δ 1.60 (1H, t, J=6.4 Hz), 4.78 (2H, d, J=6.4 Hz), 6.93-7.08 (4H, m), 7.31-7.35 (3H, m), 7.48-7.52 (2H, m). the mixture was then purged with nitrogen The reaction mixture was filtered the filtrate was then extracted with ethyl acetate concentrated purified by flash column chromatograph

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charged (2-bromo-4-fluorophenyl)methanol (954 mg, 4.65 mmol), 4-fluoro-1-vinylbenzene (1.14 g, 9.31 mmol), Pd(PPh3)2Cl2 (49 mg, 0.07 mmol), Et3N (942 mg, 9.31 mmol) and DMF (5 mL) to a sealed tube, the mixture was then purged with nitrogen, heated to 150° C. for 3 h in microwave oven. The reaction mixture was filtered, the filtrate was then extracted with ethyl acetate, concentrated and purified by flash column chromatograph to give 569 mg of the title compound (50%). 1H NMR (400 MHz, CDCl3): δ 1.60 (1H, t, J=6.4 Hz), 4.78 (2H, d, J=6.4 Hz), 6.93-7.08 (4H, m), 7.31-7.35 (3H, m), 7.48-7.52 (2H, m). the mixture was then purged with nitrogen The reaction mixture was filtered the filtrate was then extracted with ethyl acetate concentrated purified by flash column chromatograph

反応条件: temp:0.00; pressure:0.00; stir: