methyl 2,3-dichlorobenzoate

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of LiAlH4 (7.4 g, 0.195 mol) in THF (500 mL) was stirred at 0° C. A solution of methyl 2,3-dichlorobenzoate (49 g, 0.244 mol) in THF (50 mL) was added dropwise into the above mixture at 0-5° C. Then the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL), filtered and the filtrate was concentrated. The resulting residue was dissolved with DCM (500 mL) and washed with brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated to provide the titled compound (37 g, 88%), as a white solid; 1H NMR (300 MHz, CDCl3) δ ppm 4.81 (d, J=6.3 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H), 7.42-7.45 (m, 2H). Then the mixture was stirred at room temperature for 2 h The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL) filtered the filtrate was concentrated The resulting residue was dissolved with DCM (500 mL) washed with brine The organic layer was dried over Na2SO4 filtered the filtrate was concentrated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of LiAlH4 (7.4 g, 0.195 mol) in THF (500 mL) was stirred at 0° C. A solution of methyl 2,3-dichlorobenzoate (49 g, 0.244 mol) in THF (50 mL) was added dropwise into the above mixture at 0-5° C. Then the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL), filtered and the filtrate was concentrated. The resulting residue was dissolved with DCM (500 mL) and washed with brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated to provide the titled compound (37 g, 88%), as a white solid; 1H NMR (300 MHz, CDCl3) δ ppm 4.81 (d, J=6.3 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H), 7.42-7.45 (m, 2H). Then the mixture was stirred at room temperature for 2 h The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL) filtered the filtrate was concentrated The resulting residue was dissolved with DCM (500 mL) washed with brine The organic layer was dried over Na2SO4 filtered the filtrate was concentrated

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

実験手順: A solution of 2,3-dichlorobenzoic acid (100 g, 0.526 mol) in methanol (1 L), was added H2SO4 (20 mL). The solution was stirred under reflux overnight. The reaction mixture was cooled and concentrated. The resulting residue was diluted with water (100 mL) and ethyl acetate (1 L). Then the organic layer was washed with aq. NaHCO3 and brine, dried over Na2SO4, filtered and the filtrate was concentrated to provide the titled compound (99 g, 92%), as a white solid; 1H NMR (300 MHz, CDCl3) δ ppm 3.95 (s, 3H), 7.27 (t, J=7.8 Hz, 1H), 7.60 (dd, J=1.8, 7.8 Hz, 1H), 7.66 (dd, J=1.8, 7.8 Hz, 1H). under reflux overnight The reaction mixture was cooled concentrated The resulting residue was diluted with water (100 mL) and ethyl acetate (1 L) Then the organic layer was washed with aq. NaHCO3 and brine dried over Na2SO4 filtered the filtrate was concentrated

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

実験手順: To lithium diisopropyl amide (20 mL, 1.5 M in cyclohexane, 30 mmol) in THF (50.0 mL) at −78° C. was added a solution of 3-picoline (2.79 g, 30 mmol) in THF (25.0 mL) drop wise and stirred at −78° C. for 0.5 hours. The dry ice bath was removed and the reaction mixture was stirred at room temperature 1 hour. The mixture was then cooled to 0° C. and a solution of methyl 2,3-dichlorobenzoate (6.15 g, 30 mmol) in THF (25.0 mL) was added drop wise. The reaction mixture was warmed to room temperature and stirred overnight. The reaction was quenched with ammonium chloride and extracted with ethyl acetate (2×). Combined ethyl acetate phase was washed with brine, dried over magnesium sulfate and concentrated. Purification by chromatography on silica gel (70% ethyl acetate/hexane) gave 1-(2,3-dichlorophenyl)-2-(pyridin-3-yl)ethanone (1.07 g, 13%) as brown oil. The dry ice bath was removed the reaction mixture was stirred at room temperature 1 hour The mixture was then cooled to 0° C. The reaction mixture was warmed to room temperature stirred overnight The reaction was quenched with ammonium chloride extracted with ethyl acetate (2×) Combined ethyl acetate phase was washed with brine dried over magnesium sulfate concentrated Purification by chromatography on silica gel (70% ethyl acetate/hexane)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of LiAlH4 (7.4 g, 0.195 mol) in THF (500 mL) was stirred at 0° C. A solution of methyl 2,3-dichlorobenzoate (49 g, 0.244 mol) in THF (50 mL) was added dropwise into the above mixture at 0-5° C. Then the mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL), filtered and the filtrate was concentrated. The resulting residue was dissolved with DCM (500 mL) and washed with brine. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated to provide the titled compound (37 g, 88%), as a white solid; 1H NMR (300 MHz, CDCl3) δ ppm 4.81 (d, J=6.3 Hz, 2H), 7.24 (t, J=7.8 Hz, 1H), 7.42-7.45 (m, 2H). Then the mixture was stirred at room temperature for 2 h The reaction mixture was quenched with ethyl acetate (15 mL), water (7.5 mL), 15% NaOH (7.5 mL) and water (22.5 mL) filtered the filtrate was concentrated The resulting residue was dissolved with DCM (500 mL) washed with brine The organic layer was dried over Na2SO4 filtered the filtrate was concentrated

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

実験手順: A solution of 2,3-dichlorobenzoic acid (100 g, 0.526 mol) in methanol (1 L), was added H2SO4 (20 mL). The solution was stirred under reflux overnight. The reaction mixture was cooled and concentrated. The resulting residue was diluted with water (100 mL) and ethyl acetate (1 L). Then the organic layer was washed with aq. NaHCO3 and brine, dried over Na2SO4, filtered and the filtrate was concentrated to provide the titled compound (99 g, 92%), as a white solid; 1H NMR (300 MHz, CDCl3) δ ppm 3.95 (s, 3H), 7.27 (t, J=7.8 Hz, 1H), 7.60 (dd, J=1.8, 7.8 Hz, 1H), 7.66 (dd, J=1.8, 7.8 Hz, 1H). under reflux overnight The reaction mixture was cooled concentrated The resulting residue was diluted with water (100 mL) and ethyl acetate (1 L) Then the organic layer was washed with aq. NaHCO3 and brine dried over Na2SO4 filtered the filtrate was concentrated