2-氟-3-溴甲基苯甲酸甲酯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 3-(bromomethyl)-2-fluorobenzoate (11.5 g, 46.4 mmol) from Step B above and solid sodium bicarbonate (33.0 g, 398.7 mmol) in DMSO (150 mL) was refluxed until the reaction was complete by TLC (2-3 h). The mixture was cooled in an ice bath immediately and then partitioned between brine and ethyl acetate. The combined organics were concentrated and purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate) to afford methyl 2-fluoro-3-formylbenzoate as a white solid (5.44 g, 64%): 1H NMR (300 MHz, CDCl3) δ 10.43 (s, 1H), 8.21 (t, J=7.8 Hz, 1H), 8.07 (t, J=6.0 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 3.93 (s, 3H). was refluxed until the reaction was complete by TLC (2-3 h) The mixture was cooled in an ice bath immediately partitioned between brine and ethyl acetate The combined organics were concentrated purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 3-(bromomethyl)-2-fluorobenzoate (11.5 g, 46.4 mmol) from Step B above and solid sodium bicarbonate (33.0 g, 398.7 mmol) in DMSO (150 mL) was refluxed until the reaction was complete by TLC (2-3 h). The mixture was cooled in an ice bath immediately and then partitioned between brine and ethyl acetate. The combined organics were concentrated and purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate) to afford methyl 2-fluoro-3-formylbenzoate as a white solid (5.44 g, 64%): 1H NMR (300 MHz, CDCl3) δ 10.43 (s, 1H), 8.21 (t, J=7.8 Hz, 1H), 8.07 (t, J=6.0 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 3.93 (s, 3H). was refluxed until the reaction was complete by TLC (2-3 h) The mixture was cooled in an ice bath immediately partitioned between brine and ethyl acetate The combined organics were concentrated purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-fluoro-3-methylbenzoate (13.8 g, 82.3 mmol) from Step A above and N-bromosuccinimide (16.0 g, 90.6 mmol) in carbon tetrachloride (82 mL) at room temperature was added a catalytic amount of benzoyl peroxide. The yellow mixture was heated under reflux until the reaction was complete by TLC (overnight) and then it was concentrated and purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate) to afford methyl 3-(bromomethyl)-2-fluorobenzoate as a light yellow oil (11.5 g, 56%): 1H NMR (500 MHz, CDCl3) δ 7.90 (t, J=8.0 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H), 4.53 (s, 2H), 3.90 (s, 3H). The yellow mixture was heated under reflux until the reaction was complete by TLC (overnight) it was concentrated purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate)

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dimethylsulfoxide was degassed with argon for 1 h. Methyl 3-(bromomethyl)-2-fluorobenzoate (3.6 g, 14.5 mmol) from Step B above and solid sodium bicarbonate (10.5 g, 124.6 mmol) were added to the DMSO and the mixture was heated at 115° C. for 2 h. The reaction mixture was then diluted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes) to give methyl 2-fluoro-3-formylbenzoate (1.8 g, 67%): 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H), 8.22-8.19 (m, 1H), 8.09-8.06 (m, 1H), 7.37-7.34 (m, 1H), 3.98 (s, 3H). Dimethylsulfoxide was degassed with argon for 1 h washed with brine dried (Na2SO4) filtered concentrated under reduced pressure purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes)

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dimethylsulfoxide was degassed with argon for 1 h. Methyl 3-(bromomethyl)-2-fluorobenzoate (3.6 g, 14.5 mmol) from Step B above and solid sodium bicarbonate (10.5 g, 124.6 mmol) were added to the DMSO and the mixture was heated at 115° C. for 2 h. The reaction mixture was then diluted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes) to give methyl 2-fluoro-3-formylbenzoate (1.8 g, 67%): 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H), 8.22-8.19 (m, 1H), 8.09-8.06 (m, 1H), 7.37-7.34 (m, 1H), 3.98 (s, 3H). Dimethylsulfoxide was degassed with argon for 1 h washed with brine dried (Na2SO4) filtered concentrated under reduced pressure purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes)

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dimethylsulfoxide was degassed with argon for 1 h. Methyl 3-(bromomethyl)-2-fluorobenzoate (3.6 g, 14.5 mmol) from Step B above and solid sodium bicarbonate (10.5 g, 124.6 mmol) were added to the DMSO and the mixture was heated at 115° C. for 2 h. The reaction mixture was then diluted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes) to give methyl 2-fluoro-3-formylbenzoate (1.8 g, 67%): 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H), 8.22-8.19 (m, 1H), 8.09-8.06 (m, 1H), 7.37-7.34 (m, 1H), 3.98 (s, 3H). Dimethylsulfoxide was degassed with argon for 1 h washed with brine dried (Na2SO4) filtered concentrated under reduced pressure purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of methyl 3-(bromomethyl)-2-fluorobenzoate (11.5 g, 46.4 mmol) from Step B above and solid sodium bicarbonate (33.0 g, 398.7 mmol) in DMSO (150 mL) was refluxed until the reaction was complete by TLC (2-3 h). The mixture was cooled in an ice bath immediately and then partitioned between brine and ethyl acetate. The combined organics were concentrated and purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate) to afford methyl 2-fluoro-3-formylbenzoate as a white solid (5.44 g, 64%): 1H NMR (300 MHz, CDCl3) δ 10.43 (s, 1H), 8.21 (t, J=7.8 Hz, 1H), 8.07 (t, J=6.0 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 3.93 (s, 3H). was refluxed until the reaction was complete by TLC (2-3 h) The mixture was cooled in an ice bath immediately partitioned between brine and ethyl acetate The combined organics were concentrated purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of methyl 2-fluoro-3-methylbenzoate (13.8 g, 82.3 mmol) from Step A above and N-bromosuccinimide (16.0 g, 90.6 mmol) in carbon tetrachloride (82 mL) at room temperature was added a catalytic amount of benzoyl peroxide. The yellow mixture was heated under reflux until the reaction was complete by TLC (overnight) and then it was concentrated and purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate) to afford methyl 3-(bromomethyl)-2-fluorobenzoate as a light yellow oil (11.5 g, 56%): 1H NMR (500 MHz, CDCl3) δ 7.90 (t, J=8.0 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 7.19 (t, J=7.5 Hz, 1H), 4.53 (s, 2H), 3.90 (s, 3H). The yellow mixture was heated under reflux until the reaction was complete by TLC (overnight) it was concentrated purified by column chromatography (silica gel, 9:1 hexanes/ethyl acetate)

反应条件: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dimethylsulfoxide was degassed with argon for 1 h. Methyl 3-(bromomethyl)-2-fluorobenzoate (3.6 g, 14.5 mmol) from Step B above and solid sodium bicarbonate (10.5 g, 124.6 mmol) were added to the DMSO and the mixture was heated at 115° C. for 2 h. The reaction mixture was then diluted with ethyl acetate, washed with brine, dried (Na2SO4), filtered, concentrated under reduced pressure and purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes) to give methyl 2-fluoro-3-formylbenzoate (1.8 g, 67%): 1H NMR (500 MHz, CDCl3) δ 10.43 (s, 1H), 8.22-8.19 (m, 1H), 8.09-8.06 (m, 1H), 7.37-7.34 (m, 1H), 3.98 (s, 3H). Dimethylsulfoxide was degassed with argon for 1 h washed with brine dried (Na2SO4) filtered concentrated under reduced pressure purified by column chromatography (silica gel, 0% to 2% ethyl acetate in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a mixture of methyl 2-fluoro-3-methylbenzoate (1.5 g, 8.9 mmol) and N-bromosuccinimide (1.67 g, 9.4 mmol) was added carbon tetrachloride (24 mL) and benzoyl peroxide (5 mg), and the mixture was heated at reflux for 16 h. The reaction mixture was cooled, filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, eluent 5:95 to 60:40 EtOAc/hexanes) afforded methyl 3-bromomethyl-2-fluorobenzoate as a light yellow solid (0.91 g, 41%): 1H NMR (300 MHz, CDCl3) δ 7.93-7.88 (m, 1H), 7.61-7.56 (m, 1H), 7.20 (t, J=8 Hz, 1H), 4.53 (d, J=3 Hz, 2H), 3.94 (s, 3H). the mixture was heated at reflux for 16 h The reaction mixture was cooled filtered concentrated under reduced pressure Purification by flash column chromatography (silica, eluent 5:95 to 60:40 EtOAc/hexanes)